Publications by authors named "Fatih Ozaltin"

110 Publications

LONG TERM RENAL SURVIVAL OF PEDIATRIC PATIENTS WITH LUPUS NEPHRITIS.

Nephrol Dial Transplant 2021 Apr 7. Epub 2021 Apr 7.

Department of Pediatrics, Division of Nephrology, Hacettepe University Faculty of Medicine Ankara, Turkey.

Background: Childhood-onset systemic lupus erythematosus (SLE) is more severe than adult-onset disease, including more frequent kidney involvement. This study aimed to investigate baseline clinical features, treatment modalities, short- and long-term renal outcomes of pediatric patients with lupus nephritis (LN).

Materials And Methods: This study enrolled 53 LN patients out of 102 childhood-onset SLE patients followed at Hacettepe University between 2000-2020. The demographic and clinical data were reviewed retrospectively from the medical charts and electronic records. All SLE patients with renal involvement underwent renal biopsy either at the time of diagnosis or during follow-up.

Results: The median age at onset of SLE was 13.3 (IQR : 10.4-15.8) years. The median follow-up duration was 43.1 (IQR : 24.3-69.3) months. Of the 102 SLE patients, 53 patients (52%) had lupus nephritis (LN). The most frequent histopathological class was class IV LN (54.7%), followed by class III LN (22.6%). The proportion of patients who achieved either complete or partial remission were 77.3% and 73% at 6 and 12 months, respectively. In the overall LN cohort, 5- and 10-year renal survival rates were 92% and 85.7%, respectively. The remission rate at 6th month was significantly higher in Mycophenolate mofetil (MMF) and Cyclophosphamide (CYC) treated groups than other combination therapies (p = 0.02). Although no difference was found between the CYC and MMF response rates (p = 0.57), in the proliferative LN (Class III and IV), the vast majority of class IV patients (%79) received CYC as induction threapy. There was no difference between the response rates in any treatment regimens at 12th month (p = 0.56). In the multivariate analysis; male gender, requiring dialysis at the time of LN diagnosis, failure to achieve remission at 6th and at 12 th months were found to be associated with poor renal outcome.

Conclusion: Our study demonstrated that male gender, failure to achieve remission at 6th and at 12 th months, and requiring dialysis at the time of diagnosis were the best predictors of poor renal outcome. Therefore, appropriate and agressive management of pediatric LN is essential to achieve and maintain remisson.
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http://dx.doi.org/10.1093/ndt/gfab152DOI Listing
April 2021

-related Renal Tubular Dysgeneses May Not Be Fatal.

Kidney Int Rep 2021 Mar 13;6(3):846-852. Epub 2020 Dec 13.

Nephrogenetics Laboratory, Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Sihhiye, Ankara, Turkey.

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http://dx.doi.org/10.1016/j.ekir.2020.11.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938057PMC
March 2021

Management of congenital nephrotic syndrome: consensus recommendations of the ERKNet-ESPN Working Group.

Nat Rev Nephrol 2021 04 29;17(4):277-289. Epub 2021 Jan 29.

Division of Nephrology and Dialysis, Department of Pediatric Subspecialties, Bambino Gesù Pediatric Hospital Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Rome, Italy.

Congenital nephrotic syndrome (CNS) is a heterogeneous group of disorders characterized by nephrotic-range proteinuria, hypoalbuminaemia and oedema, which manifest in utero or during the first 3 months of life. The main cause of CNS is genetic defects in podocytes; however, it can also be caused, in rare cases, by congenital infections or maternal allo-immune disease. Management of CNS is very challenging because patients are prone to severe complications, such as haemodynamic compromise, infections, thromboses, impaired growth and kidney failure. In this consensus statement, experts from the European Reference Network for Kidney Diseases (ERKNet) and the European Society for Paediatric Nephrology (ESPN) summarize the current evidence and present recommendations for the management of CNS, including the use of renin-angiotensin system inhibitors, diuretics, anticoagulation and infection prophylaxis. Therapeutic management should be adapted to the clinical severity of the condition with the aim of maintaining intravascular euvolaemia and adequate nutrition, while preventing complications and preserving central and peripheral vessels. We do not recommend performing routine early nephrectomies but suggest that they are considered in patients with severe complications despite optimal conservative treatment, and before transplantation in patients with persisting nephrotic syndrome and/or a WT1-dominant pathogenic variant.
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http://dx.doi.org/10.1038/s41581-020-00384-1DOI Listing
April 2021

Determinants of outcomes in chronic pediatric peritoneal dialysis: a single center experience.

Turk J Pediatr 2020 ;62(6):940-948

Deparments of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Background: In situations where it may take a long time to perform renal transplantation peritoneal dialysis may become a long-term maintenance treatment, especially in countries with low donor rates. Therefore, we aimed to evaluate peritonitis, catheter revision and survival rates in children on chronic peritoneal dialysis (CPD); and to define related factors in a single tertiary center from a WHO upper middle income country.

Methods: Between January 1998 and September 2018, data of pediatric patients receiving CPD with a followup longer than 3 months were retrospectively analyzed. Demographic, clinical and catheter-related data were collected. Patients were grouped as being operated before/after 2009 in order to evaluate the effects of 2 different periods on outcomes.

Results: A total of 229 catheters in 132 patients were included in the study. The female to male ratio was 60/72. The mean age at the time of dialysis was 8.9 ± 5.5 years. The median follow-up period was 22.5 months (IQR 8.25-50; range 3-139). Peritonitis incidence in 1998-2008 and 2009-2018 periods was 0.13 episodes/patient-year and 0.09 episodes/ patient-year, respectively. The overall revision rate was 1 per 46.7 patient-months. Peritonitis history was the only independent risk factor for access revision (p=0.003). Peritoneal dialysis failure was observed in 25% (33/132) of patients. The need for catheter revision due to any cause, the presence of peritonitis, history of HD and infancy were independent risk factors for PD failure. The overall mortality rate was 15.2%(20/132). Having a history of temporary PD catheter placement and being infant were independent risk factors for mortality.

Conclusions: Access revision is still an important complication leading to PD failure despite the development of surgical techniques. Peritonitis is the most important cause of access revision and PD failure.
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http://dx.doi.org/10.24953/turkjped.2020.06.005DOI Listing
January 2020

Transplantation in pediatric aHUS within the era of eculizumab therapy.

Pediatr Transplant 2021 May 20;25(3):e13914. Epub 2020 Nov 20.

Department of Pediatrics, Division of Pediatric Nephrology, Gazi University School of Medicine, Ankara, Turkey.

aHUS is caused by the over-activation and dysregulation of the alternative complement pathway. Data regarding outcomes of pediatric aHUS patients after kidney transplantation are still very scarce. Accordingly, the aim of this study was to describe the clinical findings and outcomes of pediatric aHUS patients after renal transplantation. This is a retrospective, multicenter study including 12 patients from the national registry system. Among the 12 patients, eight had received prophylactic eculizumab and none of those patients (except one) had experienced aHUS recurrence during a median follow-up period of 58.5 (min-max, 4-94) months. Although eculizumab had been started on the day before transplantation in one of them, aHUS recurrence occurred during the transplantation procedure. Eculizumab had been stopped in only one patient who had no complement gene mutation after 35 months of therapy, and recurrence had not been observed during the 19 months of follow-up. In three patients, maintenance doses had been spaced out without any recurrence. One additional patient with anti-CFH antibody received only two doses of eculizumab for transplantation and had been followed for 46 months without aHUS recurrence. The remaining three patients had not received anti-C5 therapy and none of those patients experienced aHUS recurrence during a median follow-up period of 21 (min-max, 9-42) months. Prophylactic eculizumab is a safe and effective treatment for the prevention of aHUS recurrence. Eculizumab interval prolongation, discontinuation, and transplantation without eculizumab prophylaxis can be tried in selected patients with close follow-up.
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http://dx.doi.org/10.1111/petr.13914DOI Listing
May 2021

Clinical characteristics of children with congenital anomalies of the kidney and urinary tract and predictive factors of chronic kidney disease.

Turk J Pediatr 2020 ;62(5):746-755

Division of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Background: Congenital anomalies of kidney and urinary tract (CAKUT) are the leading causes of chronic kidney disease (CKD) in childhood. Determining the clinical course, outcome, and prognostic factors of this heterogeneous disease group is important to provide appropriate management and follow-up. Therefore, we aimed to identify the risk factors of CKD in CAKUT and the differences in clinical courses between disease subgroups.

Methods: Three hundred patients (M/F: 203/97) divided into 16 CAKUT categories were enrolled in the study. Logistic regression and survival analyses were performed to determine the risk factors for CKD that is defined as estimated GFR (eGFR) lower than 90 ml/min/1.73 m2 for at least 6 months.

Results: The median age of the study population at the time of the diagnosis was 0.6 years (IQR; 0.1-4.0 years). Among available prenatal diagnoses (n= 138), hydronephrosis (HN) (n= 83; 60.1%) and multicystic dysplastic kidney (MCDK) (n= 39; 28.2%) were the most frequently encountered ones. A total of 24 patients had CKD, and 13 of them (54.1%) progressed to end stage renal disease (ESRD). Patients with posterior urethral valve (PUV) had CKD and ESRD more frequently when compared to the other diagnostic groups (p < 0.001 for CKD, and p < 0.001 for ESRD). Furthermore, the PUV subgroup progressed to ESRD (median 3.63 years) earlier than the other subgroups. The diagnosis of PUV, proteinuria on the first admission, vesicoureteral reflux, and oligohydramnios were identified as independent predictors for CKD in the multivariate logistic regression analysis.

Conclusions: Knowing predictive factors for CKD in patients with CAKUT is valuable for physicians in order to determine appropriate treatment strategies and prognosis.
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http://dx.doi.org/10.24953/turkjped.2020.05.005DOI Listing
January 2020

Predictors for the use of herbal and dietary supplements in children and adolescents with kidney and urinary tract diseases.

Eur J Pediatr 2021 Jan 6;180(1):253-262. Epub 2020 Aug 6.

Division of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Sihhiye, 06100, Ankara, Turkey.

Complementary and alternative medicine are treatments administered alone or in combination with conventional medical treatments. Data on complementary and alternative medicine use in children with kidney and urinary tract diseases are limited. In this cross-sectional study, the frequency and preferred methods of complementary and alternative medicine use and factors associated with their use were evaluated in 201 patients (48% female; median age, 11 years; median disease duration, 5.1 years) with kidney and urinary tract diseases and 260 healthy (without chronic disease) controls. Data were collected through a questionnaire-based interview and patients' medical records. Herbal and dietary supplements, including fish oil, were the most commonly used complementary and alternative medicine agents in both groups. There was no difference in herbal and dietary supplement use between the groups when fish oil was excluded (29% vs. 28%; p = 0.88). Herbal and dietary supplements were mainly used to improve/mitigate renal disease (52%). Logistic regression analysis revealed that disease duration > 7 years (odds ratio (OR), 3.70; 95% confidence interval (CI), 1.48-9.20), current use of six or more drugs (OR, 5.6; 95% CI, 1.28-24.41), and recurrent urinary tract infection or nephrolithiasis (OR, 3.92; 95% CI, 1.02-15.09) were the independent risk factors for herbal and dietary supplement use, except fish oil. Middle socioeconomic status was associated with decreased herbal and dietary supplement use, except fish oil, compared with low socioeconomic status (OR, 0.30; 95% CI, 0.11-0.81). Herbal and dietary supplements were used by 78% patients, despite knowing that these products could have side effects; only 42% of the patients shared the information about herbal and dietary supplement use with their doctors.Conclusion: Herbal and dietary supplement use is frequent in children with kidney and urinary tract diseases. Educating health professionals regarding such use is mandatory for developing strategies to prevent critical consequences. What is Known: • Complementary and alternative medicine (CAM) practices are therapeutic approaches that do not have sufficient efficacy and safety evidence. • CAM is widely used in healthy children and in certain chronic diseases. What is New: • Herbal and dietary supplements (HDSs) were the most commonly used method in kidney and urinary tract diseases. • Duration of disease, number of drugs, and socioeconomic status are determinants of HDS use except fish oil.
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http://dx.doi.org/10.1007/s00431-020-03757-7DOI Listing
January 2021

Cystinosis beyond kidneys: gastrointestinal system and muscle involvement.

BMC Gastroenterol 2020 Jul 29;20(1):242. Epub 2020 Jul 29.

Department of Radiology, Hacettepe University School of Medicine, Ankara, Turkey.

Background: Cystinosis is a multisystemic disease resulting from cystine accumulation primarily in kidney and many other tissues. We intended to study the evolution of less commonly seen extrarenal complications of cystinosis in a group of patients who have periods without cysteamine treatment.

Methods: Gastrointestinal and muscular complications of cystinosis were studied in a group of 21 patients.

Results: Twenty one patients were included in the study. Among them, 14 were homozygous and 3 were compound heterozygous for CTNS mutations. The median age of diagnosis was 15 months (range; 5 months-14 years) and the mean age at last visit was 11.3 ± 6.5 years. Nine patients (42%) had end stage renal disease at a mean age of 10.6 years (6.5-17 years). Abdominal ultrasonography and portal vein doppler ultrasonography were performed in19 patients, 14 of them (74%) had hepatomegaly, 10 patients (53%) had granular pattern or heterogeneity of liver. Only one patient had high transaminase levels and liver biopsy showed cystine crystals in the liver. Eleven patients (58%) had borderline or increased portal vein minimum and maximum flow velocities. One patient had CK level of 9024 U/L and electromyographic study showed active myopathic involvement. Two patients were found to have gastroesaphageal reflux only and 4 patients were found to have esophageal remnants in addition to reflux.

Conclusions: In addition to renal functions, extrarenal organs may be affected from cystine accumulation even in childhood, especially in patients who are incompliant to treatment, resulting in complications such as swallowing difficulty, hepatomegaly and portal hypertension.
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http://dx.doi.org/10.1186/s12876-020-01385-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392712PMC
July 2020

A homozygous HOXA11 variation as a potential novel cause of autosomal recessive congenital anomalies of the kidney and urinary tract.

Clin Genet 2020 10;98(4):390-395

Nephrogenetics Laboratory, Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Congenital anomalies of the kidney and urinary tract (CAKUT) is the leading cause of end-stage kidney disease in children. Until now, more than 50 monogenic causes for CAKUT have been described, all of which only explain 10% to 20% of all patients with CAKUT, suggesting the presence of additional genes that cause CAKUT when mutated. Herein, we report two siblings of a consanguineous family with CAKUT, both of which rapidly progressed to chronic kidney disease in early childhood. Whole-exome sequencing followed by homozygosity mapping identified a homozygous variation in HOXA11. We therefore showed for the first time an association between a homozygous HOXA11 variation with CAKUT in humans, expanding the genetic spectrum of the disease.
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http://dx.doi.org/10.1111/cge.13813DOI Listing
October 2020

Genetic aspects of congenital nephrotic syndrome: a consensus statement from the ERKNet-ESPN inherited glomerulopathy working group.

Eur J Hum Genet 2020 10 28;28(10):1368-1378. Epub 2020 May 28.

Department of Pediatric Nephrology, Reference Center for Hereditary Kidney Diseases (MARHEA), Necker Hospital, APHP, 75015, Paris, France.

Congenital nephrotic syndrome (CNS) is a heterogeneous group of disorders presenting with massive proteinuria within the first 3 months of life almost inevitably leading to end-stage kidney disease. The Work Group for the European Reference Network for Kidney Diseases (ERKNet) and the European Society for Pediatric Nephrology (ESPN) has developed consensus statement on genetic aspects of CNS diagnosis and management. The presented expert opinion recommends genetic diagnostics as the key diagnostic test to be ordered already during the initial evaluation of the patient, discusses which phenotyping workup should be performed and presents known genotype-phenotype correlations.
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http://dx.doi.org/10.1038/s41431-020-0642-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608398PMC
October 2020

Renal Biopsy Prognostic Findings in Children With Atypical Hemolytic Uremic Syndrome.

Pediatr Dev Pathol 2020 Sep-Oct;23(5):362-371. Epub 2020 May 14.

Department of Pediatric Nephrology, Gazi University School of Medicine, Ankara, Turkey.

Background: The aim of this study was to investigate the histopathological findings in kidney biopsies in children with atypical hemolytic uremic syndrome (aHUS) and to determine whether specific pathological findings in aHUS have a prognostic value.

Methods: Renal biopsy specimens of 29 patients who were recorded in the national Turkish aHUS registry database were available for review. Histopathological findings were compared with the clinical and laboratory features at the presentation and the final outcome.

Results: The mean age at presentation and follow-up period was 4.9 ± 3.9 and 3.9 ± 3.0 years, respectively. The median time interval from the first symptom to biopsy was 10 days. Vascular thrombosis and interstitial fibrosis were significantly related to chronic kidney disease (CKD) requiring dialysis or kidney transplantation during follow-up (5.6-fold, for both). Glomerular necrosis, cortical necrosis, and glomerular sclerosis were markedly associated with CKD without dialysis (6.2-fold, 13.3-fold, and 8.8-fold, respectively). However, presence of endothelial swelling, subendothelial widening, and fragmented erythrocytes was found to be correlated with a favorable final outcome.

Conclusions: Presence of vascular thrombosis, cortical necrosis, and glomerular sclerosis in histopathological evaluation correlated with developing CKD. Chronic changes in the interstitial compartment were also related to poor prognosis, a finding that has been shown for the first time in pediatric aHUS cases.
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http://dx.doi.org/10.1177/1093526620925947DOI Listing
May 2020

COL4A3 mutation is an independent risk factor for poor prognosis in children with Alport syndrome.

Pediatr Nephrol 2020 10 11;35(10):1941-1952. Epub 2020 May 11.

Division of Pediatric Nephrology, Faculty of Medicine, Hacettepe University, 06230, Ankara, Turkey.

Background: Alport syndrome (AS) is an inherited glomerular disease caused by mutations in COL4A3, COL4A4, or COL4A5. Associations between clinical manifestations and genotype are not yet well defined. Our study aimed to define clinical and genetic characteristics, establish genotype-phenotype correlations, and determine prognosis of AS in children.

Methods: A total of 87 children with AS from 10 pediatric nephrology centers, whom had genetic analyses performed at the Hacettepe University Nephrogenetics Laboratory between February 2017 and February 2019, were included. Data regarding demographics, family history, clinical and laboratory characteristics, histopathological and genetic test results, treatments, and yearly follow-up results were retrospectively analyzed.

Results: Of 87 patients, 16% presented with nephrotic syndrome. In patients with nephrotic syndrome, kidney biopsy findings showed focal segmental glomerulosclerosis (FSGS) in 79%, and COL4A3 mutations were the leading genetic abnormality (50%). Twenty-four percent of all patients progressed to chronic kidney disease (CKD). The rate of progression to CKD and the decline in the glomerular filtration rate of the patients with COL4A3 mutation were higher than other mutation groups (p < 0.001 and p = 0.04, respectively). In kidney survival analysis, nephrotic syndrome presentation, histopathology of FSGS, COL4A3 mutations, and autosomal recessive inheritance were found as independent risk factors for earlier progression to CKD. Cyclosporin A treatment did not improve kidney survival.

Conclusions: We emphasize that genetic testing is important for patients suspected as having AS. Furthermore, COL4A mutations should be considered in patients with FSGS and steroid-resistant nephrotic syndrome. This approach will shed light on the prognosis of patients and help with definitive diagnosis, preventing unnecessary and potentially harmful medications. Graphical abstract.
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http://dx.doi.org/10.1007/s00467-020-04574-8DOI Listing
October 2020

Long-term follow-up results of patients with ADCK4 mutations who have been diagnosed in the asymptomatic period: effects of early initiation of CoQ10 supplementation.

Turk J Pediatr 2019 ;61(5):657-663

Division of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara.

Atmaca M, Gülhan B, Atayar E, Karabay Bayazıt A, Candan C, Arıcı M, Topaloğlu R, Özaltın F. Long-term follow-up results of patients with ADCK4 mutations who have been diagnosed in the asymptomatic period: effects of early initiation of CoQ10 supplementation. Turk J Pediatr 2019; 61: 657-663. ADCK4-related glomerulopathy is a recently recognized clinical entity associated with insidious onset in young children and a high potential to progress to chronic kidney disease in adolescents. Early initiation of exogenous coenzyme Q10 (CoQ10) supplementation in the asymptomatic period could be protective on renal functions. In the present study, we aimed to investigate long-term follow-up of patients that we have diagnosed during the asymptomatic period and in whom we started CoQ10 treatment. We analyzed long-term effects of CoQ10 on proteinuria and estimated glomerular filtration rate (eGFR) in this patient population. A total of 8 patients (4 female, 4 male) from 6 different families were included. The mean age at diagnosis and at last visit were 16.8±11.2 years and 20.7±11.7 years, respectively. None of the patients had extrarenal system involvement. At the time of initiation of treatment; median eGFR was 107.8 ml/min/1.73 m2, median proteinuria was 1008 mg/m2/day. After a median follow-up period of 25.3±5.8 months, median proteinuria decreased to 318.5 mg/m2/day (p=0.03) and median eGFR remained stable at 99.6 ml/min/1.73 m2 (p=0.21). Coenzyme Q10 treatment is effective for reducing proteinuria and seems to be renoprotective.
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http://dx.doi.org/10.24953/turkjped.2019.05.003DOI Listing
July 2020

Surgical management of renovascular hypertension in children and young adults: a 13-year experience.

Interact Cardiovasc Thorac Surg 2019 11;29(5):746-752

Department of Cardiovascular Surgery, Hacettepe University Hospital, Ankara, Turkey.

Objectives: In this study, we aimed to evaluate the early and mid-term outcomes of surgery for renovascular hypertension (RVH) at our institution, within the last 13 years.

Methods: We retrospectively reviewed 19 patients who underwent surgery for RVH, between 2005 and 2017. The age at operation, clinical characteristics, cause of arterial stenosis, diagnostic workup, surgical management and outcomes during the follow-up were analysed. The continuous variables were expressed as mean ± standard deviation.

Results: Twelve female and 7 male patients underwent surgery for RVH. Their mean age was 17.07 ± 11.9 years (range 4-42 years). Nine patients had renal arterial stenosis, and 10 patients had midaortic syndrome (MAS). Aortorenal bypass with the saphenous vein was performed in 6 patients with renal arterial stenosis and 1 patient with MAS. An isolated thoracic aorta-abdominal aortic bypass was performed in 1 patient with MAS, and thoracic aorta-abdominal aortic bypass combined with unilateral aortarenal bypass was performed in 9 patients with MAS. The other surgical procedures performed were 2 autotransplantations and 2 unilateral nephrectomies. Among the patients with MAS, 4 underwent reoperation. The mean follow-up duration was 45.58 ± 32.7 months. Hypertension was cured in 3 patients and improved in 14 patients. The postoperative follow-up creatinine levels were similar to preoperative creatinine levels. All bypasses were patent on mid-term follow-up. One patient who underwent aortorenal bypass died 14 months postoperatively.

Conclusions: Surgical management is a suitable option for patients with RVH, who were unresponsive to medical and/or endovascular management. Surgical methods are safe and effective in children and young adults with RVH.
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http://dx.doi.org/10.1093/icvts/ivz157DOI Listing
November 2019

Gastric duplication cyst in an infant with Finnish-type congenital nephrotic syndrome: concurrence or coincidence?

Acta Clin Belg 2021 Apr 5;76(2):155-157. Epub 2019 Oct 5.

Department of Pediatric Nephrology, Dr Sami Ulus Maternity and Child Health and Diseases Training and Research Hospital, Ankara, Turkey.

Congenital nephrotic syndrome (CNS) is a rare disorder characterized by massive proteinuria and marked edema manifesting in utero or during the first 3 months of life. CNS can be caused by congenital infections, allo-immune maternal disease or due to the genetic defects of podocyte proteins most commonly NPHS1. Here we present a case of Finnish-type congenital nephrotic syndrome along with feeding problems and abdominal distention which was diagnosed during follow-up as a gastric-duplication cyst with a novel mutation in the nephrin gene. CNS feeding problems are attributed mainly to primary disease but in literature there are case reports of patients with CNS and hypertrophic pyloric stenosis. NPHS1 is also expressed in the stomach tissue. Physicians should be aware of this rare extra-renal manifestation or coincidence of this rare disease.
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http://dx.doi.org/10.1080/17843286.2019.1675333DOI Listing
April 2021

BK virus associated nephropathy and severe pneumonia in a kidney transplanted adolescent with Schimke immuneosseous- dysplasia.

Turk J Pediatr 2019;61(1):111-116

Department of Pediatrics Division of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Düzova A, Gülhan B, Topaloğlu R, Özaltın F, Cengiz AB, Yetimakman AF, Doğru D, Güçer Ş, Beşbaş N. BK virus associated nephropathy and severe pneumonia in a kidney transplanted adolescent with Schimke immune-osseous-dysplasia. Turk J Pediatr 2019; 61: 111-116. Patients with juvenile onset Schimke immune-osseous-dysplasia (SIOD) have less severe symptoms and can survive in the second and third decade of life. We present an 18 year-old adolescent with juvenile onset SIOD who was diagnosed after renal transplantation and developed BK virus associated nephropathy (BKVAN) and severe pneumonia during follow-up. The patient developed nephrotic syndrome, unresponsive to immunosuppressives, at the age of 8 years. He had a history of meningitis, short stature, microcephaly, prominent ears, and bilateral cryptorchidism. A renal transplantation was performed at the age of 15 years. During follow-up, he suffered from leucopenia, urinary tract infections, herpes labialis, and candida esophagitis. Sanger sequencing of SMARCAL1 revealed a missense mutation on exon 11 (R586W). A renal biopsy performed after a sharp increase in serum creatinine (without significant viremia) revealed BKVAN which responded to sirolimus monotherapy and cidofovir. Three months later, he suffered from productive cough and dyspnea with diffuse ground glass pulmonary infiltrates. His clinical situation deteriorated and non-invasive mechanical ventilation was started. Cidofovir (2 mg/kg) was re-started weekly for a possible BKV pneumonia with intravenous immunoglobulin. After 5 doses of cidofovir and intense antibiotic regime, his dyspnea resolved with stable graft functions. In our case; BKVAN, which developed without significant viremia, and possibly associated pneumonia were treated successfully with cidofovir and sirolimus monotherapy.
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http://dx.doi.org/10.24953/turkjped.2019.01.018DOI Listing
January 2020

CD80 expression and infiltrating regulatory T cells in idiopathic nephrotic syndrome of childhood.

Pediatr Int 2019 Dec 2;61(12):1250-1256. Epub 2019 Dec 2.

Division of Pediatric Nephrology, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Background: CD80 (also known as B7-1) is a co-stimulatory molecule that is expressed in biopsies and also excreted in urine in patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). CD80 is inhibited by the cytotoxic T-lymphocyte-associated-antigen 4 (CTLA4), which is mainly expressed on regulatory T cells (Tregs). Ineffective circulating Treg response is involved in the pathogenesis of nephrotic syndrome. In this study, we evaluated CD80 expression and infiltrating Tregs in children with MCD and FSGS.

Methods: Evaluation of CD80 expression and semi-quantitative evaluation of Tregs (FOXP3-positive CD4 T cells) were carried out in 31 kidney biopsies (12 MCD, 19 FSGS) with immunofluorescence and immunohistochemistry staining.

Results: All MCD sections were stained negative; whereas six out of 19 FSGS sections (all from steroid-resistant (SR) patients), including one from a Wilms' tumor 1 (WT1) mutation-positive FSGS patient, stained positive for anti-CD80 goat antibody, and negative for anti-CD80 rabbit antibody. FSGS biopsy specimens had significantly higher FOXP3-positive cells/mm compared with MCD and control samples (P < 0.001). Biopsy samples from SR-FSGS patients (n = 12) with positive CD80 staining (n = 6) had significantly less Tregs (FOXP3-positive CD4 T cells) compared with CD80 (-) biopsies (n = 6; P = 0.004).

Conclusion: CD80 expression was not detected in the majority of the archival biopsy sections and the results were not consistent across the different antibodies. In the SR-FSGS sections, however, CD80-positive biopsies had decreased FOXP3-positive CD4 T cells, suggesting that a decreased anti-inflammatory milieu may be the cause of increased CD80 expression.
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http://dx.doi.org/10.1111/ped.14005DOI Listing
December 2019

Rituximab for Children With Difficult-to-Treat Nephrotic Syndrome: Its Effects on Disease Progression and Growth.

Front Pediatr 2019 30;7:313. Epub 2019 Jul 30.

Division of Pediatric Nephrology, Department of Pediatrics, School of Medicine, Hacettepe University, Ankara, Turkey.

Since the early 2000s rituximab (RTX) has been thought of as an alternative treatment for steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS). This study aimed to determine the effects of RTX treatment on disease outcome and growth in pediatric SSNS and SRNS patients. The medical records of pediatric SSNS and SRNS patients that began RTX treatment at the mean age of 10.8 ± 5.1 years between 2009 and 2017 were retrospectively reviewed. Additionally, the effect of RTX on growth was evaluated based on patient height, weight, and BMI z scores. The study included 41 children, of which 21 had SSNS and 20 had SRNS. Mean age at diagnosis of NS was 5.8 ± 4.7 years. Mean duration of post-RTX treatment follow-up was 2.3 ± 1.6 years. Among the SSNS patients, 6 and 11 patients were steroid free and calcineurin inhibitor free at the last follow-up visit, respectively. The 1-year cumulative steroid and calcineurin inhibitor doses both decreased after RTX treatment, as compared to before RTX ( = 0.001 and = 0.015, respectively). The median height -score at the time of RTX initiation was -1.2 and the median height -score at the last follow-up visit was -0.6 ( = 0.044). The median BMI -score decreased from 1.6 (IQR; 0.9-3.0) at the time RTX was initiated to 1.1 IQR; [(-0.7)-2.5] at the last follow-up visit ( = 0.007). At the last follow-up visit 4 SRNS patients had complete remission and 4 had partial remission. The 1-year cumulative steroid dosage in the SRNS patients decreased significantly after RTX, as compared to before RTX ( = 0.001). The median height -score at the time of RTX initiation was -0.8 and the median height -score at the last follow-up visit was -0.7 ( = 0.81). The median BMI -score decreased from 0.3 at the time RTX was initiated to -0.1 at the last follow-up visit ( = 0.11). RTX has a more positive effect on disease outcome and growth in SSNS patients than in those with SRNS.
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http://dx.doi.org/10.3389/fped.2019.00313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682627PMC
July 2019

Response to Early Coenzyme Q10 Supplementation Is not Sustained in CoQ10 Deficiency Caused by CoQ2 Mutation.

Pediatr Neurol 2018 11 27;88:71-74. Epub 2018 Jul 27.

Division of Pediatric Neurology, Hacettepe University Faculty of Medicine, Ankara, Turkey. Electronic address:

Background: COQ2 mutations cause a rare infantile multisystemic disease with heterogeneous clinical features. Promising results have been reported in response to Coenzyme Q10 treatment, especially for kidney involvement, but little is known about the long-term outcomes.

Methods: We report four new patients from two families with the c.437G→A (p.Ser146Asn) mutation in COQ2 and the outcomes of two patients after long-term coenzyme Q10 treatment.

Results: Index cases from two families presented with vomiting, nephrotic range proteinuria, and diabetes in early infancy. These patients were diagnosed with coenzyme Q10 deficiency and died shortly after diagnosis. Siblings of the index cases later presented with neonatal diabetes and proteinuria and were diagnosed at the first day of life. Coenzyme Q10 treatment was started immediately. The siblings responded dramatically to coenzyme Q10 treatment with normalized glucose and proteinuria levels, but they developed refractory focal clonic seizures beginning at three months of life that progressed to encephalopathy.

Conclusions: In our cohort with CoQ10 deficiency, neurological involvement did not improve with oral coenzyme Q10 treatment despite the initial recovery from the diabetes and nephrotic syndrome.
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http://dx.doi.org/10.1016/j.pediatrneurol.2018.07.008DOI Listing
November 2018

An immunohistochemical approach to detect oncogenic CTNNB1 mutations in primary neoplastic tissues.

Lab Invest 2019 01 3;99(1):128-137. Epub 2018 Sep 3.

Departments of Internal Medicine, Human Genetics, and Pathology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.

The Wnt/β-catenin signaling pathway is dysregulated in different types of neoplasms including colorectal cancer (CRC). Aberrant activation of this signaling pathway is a key early event in the development of colorectal neoplasms, and is mainly caused by loss of function mutations in Adenomatous Polyposis Coli (APC), and less frequently by β-catenin stabilization mutations via missense or interstitial genomic deletions in CTNNB1. In this study, we have defined an immunohistochemical algorithm to dissect Wnt pathway alterations in formalin-fixed and paraffin-embedded neoplastic tissues. Basically, consecutive sections of tumor specimens were stained by immunohistochemistry with two different monoclonal antibodies against β-catenin: one (anti-active β-catenin antibody) recognizes hypo-phosphorylated β-catenin and the other recognizes the total pool of β-catenin. We validated the strategy in the HCT116 CRC cell line which has an in-frame deletion of β-catenin serine 45, and then studied human tumor microarrays containing colon adenomas, CRCs, solid pseudopapillary neoplasms of the pancreas as well as the whole tissue sections of CRCs, desmoid fibromatosis, and pilomatrixoma of the skin. In some tumors, we found strong β-catenin cytoplasmic and/or nuclear staining with the total β-catenin antibody but no staining with the anti-active β-catenin antibody. This was inferred to be an altered/mutant β-catenin staining pattern. All six colon adenomas of the 126 total adenomas studied for the altered/mutant β-catenin staining pattern had presumptively pathogenic point mutations or deletions in CTNNB1. Four of 10 CRCs with the alterated/mutant β-catenin staining pattern studied in depth, from 181 total CRCs from tissue microarray, had pathogenic CTNNB1 mutations. The frequencies of CTNNB1 alterations in non-colonic tumors with altered/mutant β-catenin staining ranged between 46 and 100%. Our results demonstrate that the immunohistochemical approach described here can detect oncogenic forms of β-catenin in primary tissue samples and can also highlight other tumors with presumptive novel defects activating the Wnt/β-catenin pathway.
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http://dx.doi.org/10.1038/s41374-018-0121-9DOI Listing
January 2019

Hemolytic uremic syndrome and IgA nephropathy in a child: Coincidence or not?

Turk J Pediatr 2018 ;60(1):81-85

Departments of Pediatric Nephrology and Rheumatology, Nephrogenetics Laboratory, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Sürmeli-Döven S, Delibaş A, Gürses İ, Kayacan UR, Coşkun-Yılmaz B, Esen K, Korkmaz E, Özaltın F. Hemolytic uremic syndrome and IgA nephropathy in a child: Coincidence or not? Turk J Pediatr 2018; 60: 81-85. A previously healthy 18-month old boy, presenting with diarrhea, anemia, thrombocytopenia and acute renal failure was admitted to our hospital. Hemolytic uremic syndrome (HUS) was diagnosed with his clinical and laboratory findings. His stool was negative for Shiga toxin producing E. coli (STEC). During follow-up he developed respiratory distress, hypertrophic cardiomyopathy and seizure. His genetic tests for atypical HUS (aHUS) were negative. His clinical and histological findings indicated hemolytic uremic syndrome and immunglobulin A nephropathy (IgAN). The patient responded to steroid treatment and plasma exchange therapy with peritoneal dialysis. We discuss the probable connection between HUS and IgAN.
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http://dx.doi.org/10.24953/turkjped.2018.01.012DOI Listing
January 2019

Persistent hypoglycemic attacks during hemodialysis sessions in an infant with congenital nephrotic syndrome: Answers.

Pediatr Nephrol 2019 01 29;34(1):77-79. Epub 2018 Jun 29.

Nephrogenetics Laboratory, Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Sihhiye, Ankara, Turkey.

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http://dx.doi.org/10.1007/s00467-018-3982-7DOI Listing
January 2019

Persistent hypoglycemic attacks during hemodialysis sessions in an infant with congenital nephrotic syndrome: Questions.

Pediatr Nephrol 2019 01 29;34(1):75-76. Epub 2018 Jun 29.

Nephrogenetics Laboratory, Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Sihhiye, Ankara, Turkey.

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http://dx.doi.org/10.1007/s00467-018-3980-9DOI Listing
January 2019

Extra-Renal manifestations of atypical hemolytic uremic syndrome in children.

Pediatr Nephrol 2018 08 2;33(8):1395-1403. Epub 2018 Apr 2.

Gazi University, School of Medicine, Department of Pediatric Nephrology, Istanbul, Turkey.

Background: Atypical hemolytic uremic syndrome (aHUS) is a chronic disease characterized by thrombotic microangiopathy and a high risk of end-stage kidney disease. Dysregulation and/or excessive activation of the complement system results in thrombotic microangiopathy. Interest in extrarenal manifestations of aHUS is increasing. This study aimed to determine the clinical characteristics of patients with extrarenal manifestations of aHUS in childhood.

Methods: This study included 70 children with extrarenal manifestations of HUS from the national Turkish aHUS Registry. The demographics, clinical characteristics, genetic test results, all treatments, and renal/hematologic status of aHUS patients with extrarenal involvement were recorded.

Results: The most common extrarenal manifestation was neurological system involvement (n = 46 [27.2%]), followed by gastrointestinal (n = 20 [11.8%]), cardiovascular (n = 12 [7%]), and respiratory (n = 12 [7%]) involvement. The patients with neurological involvement had a higher mortality rate and a lower estimated glomerular filtration rate (eGFR) than the other patients at last follow-up. Eculizumab (with or without plasma exchange/plasma infusion) treatment increased the renal and hematologic recovery rates.

Conclusions: The most common and serious extrarenal manifestation of aHUS is neurological involvement and treatment outcome findings presented herein are important to all relevant clinicians.
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http://dx.doi.org/10.1007/s00467-018-3933-3DOI Listing
August 2018

Atypical Hemolytic Uremic Syndrome in Children Aged <2 Years.

Nephron 2018 13;139(3):211-218. Epub 2018 Mar 13.

Department of Pediatric Nephrology, Ankara University Faculty of Medicine, Ankara, Turkey.

Background: There are limited data on infants with atypical hemolytic uremic syndrome (aHUS). The aim of this study was to determine the clinical and laboratory features, and to evaluate treatment modalities and outcomes in infants with aHUS.

Materials And Methods: Relevant data on patients with onset of aHUS at age <2 years were obtained from the Turkish Pediatric aHUS Registry.

Results: Among the 146 patients included in the Registry, 53 (36%) (23 male and 30 female) were enrolled for the study. Age at disease onset was ≤1 year in 29 of the patients. In all, 21 (40%) of the patients developed neurological symptoms. Disease-causing mutations were noted in 14 (36%) of the 39 patients in which genetic analysis was performed. Plasma therapy was performed in 42 (79%) patients; eculizumab therapy was administered to treat the first episode of aHUS in 33 (62%) patients and in 5 patients as the first- line therapy. In total, 38 (72%) patients received renal replacement therapy (RRT), 3 (6%) died due to acute illness, and 4 (8%) were discharged from hospital with RRT. Follow-up visit data were available for 46 patients and the median duration was 23 months (range 3-129 months). End-stage renal disease developed only in 1 patient. Proteinuria and hypertension persisted in 17 (37%) and 20 patients (44%) respectively. Eculizumab treatment was continued in 25 of the 39 patients during the follow-up period.

Conclusion: One-third of the aHUS patients had disease onset during infancy. The prognosis of this life-threatening disease seems to get better with improved treatment modalities.
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http://dx.doi.org/10.1159/000487609DOI Listing
September 2019

Nephropathic Cystinosis Mimicking Bartter Syndrome: a Novel Mutation.

Iran J Kidney Dis 2018 01;12(1):61-63

Kayseri Education and Research Hospital, Department of Pediatric Nephrology, Kayseri, Turkey.

Cystinosis is a rare autosomal recessive disorder resulting from defective lysosomal transport of cystine due to mutations in the cystinosin lysosomal cystine transporter (CTNS) gene. The clinical phenotype of nephropathic cystinosis is characterized by renal tubular Fanconi syndrome and development of end-stage renal disease during the first decade. Although metabolic acidosis is the classically prominent finding of the disease, a few cases may present with hypokalemic metabolic alkalosis mimicking Bartter syndrome. Bartter-like presentation may lead to delay in diagnosis and initiation of specific treatment for cystinosis. We report a case of a 6-year-old girl initially presenting with the features of Bartter syndrome that was diagnosed 2 years later with nephropathic cystinosis and a novel CTNS mutation.
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January 2018

Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome.

Clin J Am Soc Nephrol 2018 01 10;13(1):53-62. Epub 2017 Nov 10.

Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.

Background And Objectives: Steroid-resistant nephrotic syndrome overwhelmingly progresses to ESRD. More than 30 monogenic genes have been identified to cause steroid-resistant nephrotic syndrome. We previously detected causative mutations using targeted panel sequencing in 30% of patients with steroid-resistant nephrotic syndrome. Panel sequencing has a number of limitations when compared with whole exome sequencing. We employed whole exome sequencing to detect monogenic causes of steroid-resistant nephrotic syndrome in an international cohort of 300 families.

Design, Setting, Participants, & Measurements: Three hundred thirty-five individuals with steroid-resistant nephrotic syndrome from 300 families were recruited from April of 1998 to June of 2016. Age of onset was restricted to <25 years of age. Exome data were evaluated for 33 known monogenic steroid-resistant nephrotic syndrome genes.

Results: In 74 of 300 families (25%), we identified a causative mutation in one of 20 genes known to cause steroid-resistant nephrotic syndrome. In 11 families (3.7%), we detected a mutation in a gene that causes a phenocopy of steroid-resistant nephrotic syndrome. This is consistent with our previously published identification of mutations using a panel approach. We detected a causative mutation in a known steroid-resistant nephrotic syndrome gene in 38% of consanguineous families and in 13% of nonconsanguineous families, and 48% of children with congenital nephrotic syndrome. A total of 68 different mutations were detected in 20 of 33 steroid-resistant nephrotic syndrome genes. Fifteen of these mutations were novel. , , , and were the most common genes in which we detected a mutation. In another 28% of families, we detected mutations in one or more candidate genes for steroid-resistant nephrotic syndrome.

Conclusions: Whole exome sequencing is a sensitive approach toward diagnosis of monogenic causes of steroid-resistant nephrotic syndrome. A molecular genetic diagnosis of steroid-resistant nephrotic syndrome may have important consequences for the management of treatment and kidney transplantation in steroid-resistant nephrotic syndrome.
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http://dx.doi.org/10.2215/CJN.04120417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5753307PMC
January 2018

Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly.

Authors:
Daniela A Braun Jia Rao Geraldine Mollet David Schapiro Marie-Claire Daugeron Weizhen Tan Olivier Gribouval Olivia Boyer Patrick Revy Tilman Jobst-Schwan Johanna Magdalena Schmidt Jennifer A Lawson Denny Schanze Shazia Ashraf Jeremy F P Ullmann Charlotte A Hoogstraten Nathalie Boddaert Bruno Collinet Gaëlle Martin Dominique Liger Svjetlana Lovric Monica Furlano I Chiara Guerrera Oraly Sanchez-Ferras Jennifer F Hu Anne-Claire Boschat Sylvia Sanquer Björn Menten Sarah Vergult Nina De Rocker Merlin Airik Tobias Hermle Shirlee Shril Eugen Widmeier Heon Yung Gee Won-Il Choi Carolin E Sadowski Werner L Pabst Jillian K Warejko Ankana Daga Tamara Basta Verena Matejas Karin Scharmann Sandra D Kienast Babak Behnam Brendan Beeson Amber Begtrup Malcolm Bruce Gaik-Siew Ch'ng Shuan-Pei Lin Jui-Hsing Chang Chao-Huei Chen Megan T Cho Patrick M Gaffney Patrick E Gipson Chyong-Hsin Hsu Jameela A Kari Yu-Yuan Ke Cathy Kiraly-Borri Wai-Ming Lai Emmanuelle Lemyre Rebecca Okashah Littlejohn Amira Masri Mastaneh Moghtaderi Kazuyuki Nakamura Fatih Ozaltin Marleen Praet Chitra Prasad Agnieszka Prytula Elizabeth R Roeder Patrick Rump Rhonda E Schnur Takashi Shiihara Manish D Sinha Neveen A Soliman Kenza Soulami David A Sweetser Wen-Hui Tsai Jeng-Daw Tsai Rezan Topaloglu Udo Vester David H Viskochil Nithiwat Vatanavicharn Jessica L Waxler Klaas J Wierenga Matthias T F Wolf Sik-Nin Wong Sebastian A Leidel Gessica Truglio Peter C Dedon Annapurna Poduri Shrikant Mane Richard P Lifton Maxime Bouchard Peter Kannu David Chitayat Daniella Magen Bert Callewaert Herman van Tilbeurgh Martin Zenker Corinne Antignac Friedhelm Hildebrandt

Nat Genet 2017 Oct 14;49(10):1529-1538. Epub 2017 Aug 14.

Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms.
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http://dx.doi.org/10.1038/ng.3933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819591PMC
October 2017

Low renal but high extrarenal phenotype variability in Schimke immuno-osseous dysplasia.

PLoS One 2017 10;12(8):e0180926. Epub 2017 Aug 10.

Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany.

Schimke immuno-osseous dysplasia (SIOD) is a rare multisystem disorder with early mortality and steroid-resistant nephrotic syndrome (SRNS) progressing to end-stage kidney disease. We hypothesized that next-generation gene panel sequencing may unsurface oligosymptomatic cases of SIOD with potentially milder disease courses. We analyzed the renal and extrarenal phenotypic spectrum and genotype-phenotype associations in 34 patients from 28 families, the largest SMARCAL1-associated nephropathy cohort to date. In 11 patients the diagnosis was made unsuspectedly through SRNS gene panel testing. Renal disease first manifested at median age 4.5 yrs, with focal segmental glmerulosclerosis or minimal change nephropathy on biopsy and rapid progression to end-stage kidney disease (ESKD) at median age 8.7 yrs. Whereas patients diagnosed by phenotype more frequently developed severe extrarenal complications (cerebral ischemic events, septicemia) and were more likely to die before age 10 years than patients identified by SRNS-gene panel screening (88 vs. 40%), the subgroups did not differ with respect to age at proteinuria onset and progression to ESKD. Also, 10 of 11 children diagnosed unsuspectedly by Next Generation Sequencing were small at diagnosis and all showed progressive growth failure. Severe phenotypes were usually associated with biallelic truncating mutations and milder phenotypes with biallelic missense mutations. However, no genotype-phenotype correlation was observed for the renal disease course. In conclusion, while short stature is a reliable clue to SIOD in children with SRNS, other systemic features are highly variable. Our findings support routine SMARCAL1 testing also in non-syndromic SRNS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180926PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552097PMC
October 2017