Publications by authors named "Essam Al-Sabban"

6 Publications

  • Page 1 of 1

The morbid genome of ciliopathies: an update.

Genet Med 2020 06 14;22(6):1051-1060. Epub 2020 Feb 14.

Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Purpose: Ciliopathies are highly heterogeneous clinical disorders of the primary cilium. We aim to characterize a large cohort of ciliopathies phenotypically and molecularly.

Methods: Detailed phenotypic and genomic analysis of patients with ciliopathies, and functional characterization of novel candidate genes.

Results: In this study, we describe 125 families with ciliopathies and show that deleterious variants in previously reported genes, including cryptic splicing variants, account for 87% of cases. Additionally, we further support a number of previously reported candidate genes (BBIP1, MAPKBP1, PDE6D, and WDPCP), and propose nine novel candidate genes (CCDC67, CCDC96, CCDC172, CEP295, FAM166B, LRRC34, TMEM17, TTC6, and TTC23), three of which (LRRC34, TTC6, and TTC23) are supported by functional assays that we performed on available patient-derived fibroblasts. From a phenotypic perspective, we expand the phenomenon of allelism that characterizes ciliopathies by describing novel associations including WDR19-related Stargardt disease and SCLT1- and CEP164-related Bardet-Biedl syndrome.

Conclusion: In this cohort of phenotypically and molecularly characterized ciliopathies, we draw important lessons that inform the clinical management and the diagnostics of this class of disorders as well as their basic biology.
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June 2020

A molecular genetic analysis of childhood nephrotic syndrome in a cohort of Saudi Arabian families.

J Hum Genet 2013 Jul 18;58(7):480-9. Epub 2013 Apr 18.

Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Nephrotic syndrome (NS) is a renal disease characterized by heavy proteinuria, hypoalbuminemia, edema and hyperlipidemia. Its presentation within the first 3 months of life or in multiple family members suggests an underlying inherited cause. To determine the frequency of inherited NS, 62 cases (representing 49 families with NS) from Saudi Arabia were screened for mutations in NPHS1, NPHS2, LAMB2, PLCE1, CD2AP, MYO1E, WT1, PTPRO and Nei endonuclease VIII-like 1 (NEIL1). We detected likely causative mutations in 25 out of 49 families studied (51%). We found that the most common genetic cause of NS in our cohort was a homozygous mutation in the NPHS2 gene, found in 11 of the 49 families (22%). Mutations in the NPHS1 and PLCE1 genes allowed a molecular genetic diagnosis in 12% and 8% of families, respectively. We detected novel MYO1E mutations in three families (6%). No mutations were found in WT1, PTPRO or NEIL1. The pathogenicity of novel variants was analyzed by in silico tests and by genetic screening of ethnically matched control populations. This is the first report describing the molecular genetics of NS in the Arabian Peninsula.
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July 2013

Clinical and epidemiological assessment of steroid-resistant nephrotic syndrome associated with the NPHS2 R229Q variant.

Kidney Int 2009 Apr 14;75(7):727-35. Epub 2009 Jan 14.

INSERM, U574, Hôpital Necker, Paris, France.

Mutations of NPHS2, encoding podocin, are the main cause of autosomal recessive steroid-resistant nephrotic syndrome (NS) presenting in childhood. Adult-onset steroid-resistant NS has been described in patients heterozygous for a pathogenic NPHS2 mutation together with the p.R229Q variant. To determine the frequency and the phenotype of patients carrying the p.R229Q variant, we sequenced the complete coding region of NPHS2 in 455 families (546 patients) non-responsive to immunosuppressive therapy or without relapse after transplantation. Among affected Europeans, the p.R229Q allele was significantly more frequent compared to control individuals. Thirty-six patients from 27 families (11 families from Europe and 14 from South America) were compound heterozygotes for the p.R229Q variant and one pathogenic mutation. These patients had significantly later onset of NS and end stage renal disease than patients with two pathogenic mutations. Among 119 patients diagnosed with NS presenting after 18 years of age, 18 patients were found to have one pathogenic mutation and p.R229Q, but none had two pathogenic mutations. Our study shows that compound heterozygosity for p.R229Q is associated with adult-onset steroid-resistant NS, mostly among patients of European and South American origin. Screening for the p.R229Q variant is recommended in these patients along with further NPHS2 mutation analysis in those carrying the variant.
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April 2009

Hyperglycemia and hypoinsulinemia in patients with Fanconi-Bickel syndrome.

J Pediatr Endocrinol Metab 2008 Jun;21(6):581-6

Division of Pediatric Endocrinology, Department of Pediatrics, King Faisal Specialist Hospital & Research Centre, Jeddah, Saudi Arabia.

Unlabelled: Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by the combination of hepatorenal glycogen accumulation and Fanconi-type nephropathy. Mutations in GLUT2, the gene for facilitative glucose transporter protein 2 (GLUT2), cause FBS.

Aim: To evaluate glucose and insulin responses to oral glucose load in patients with FBS.

Methods: Ten children (7.3 +/- 4.8 years) diagnosed with FBS in early infancy underwent a standard oral glucose tolerance test (OGTT); plasma glucose (PG) and serum insulin concentrations were measured at 30-min intervals for 2 hours. HbA1c, insulin-like growth factor-I, and fasting lipid profiles were also measured.

Results: Mean fasting and 2-h PG concentrations were 3.8 +/- 0.9 mmol/l and 8.6 +/- 3.0 mmol/1, respectively. 2-hour PG levels were above 11.1 mmol/l in two patients (20%) and between 7.75 and 11.1 mmol/ in four patients (40%). HbA1c was normal in all the patients with a mean of 5.4 +/- 0.3%. Mean fasting and peak serum insulin levels were 8.7 +/- 0.8 pmol/ and 98.6 +/- 43.0 pmol/l, respectively, and did not differ between the patients with normal and abnormal OGTT. Patients with abnormal OGTT were younger (4.8 +/- 3.2 vs 11.0 +/- 4.8 yr; p = 0.04). Fasting PG increased with age (r = 0.80, p < 0.01). Total and LDL cholesterol as well as triglyceride concentrations were elevated.

Conclusions: Most but not all patients with FBS have impaired glucose tolerance/diabetes range hyperglycemia after OGTT while maintaining normal HbA1c. Patients with FBS are relatively hypoinsulinemic. Both fasting hypoglycemia and post-OGTT hyperglycemia seem to improve with age.
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June 2008

Post renal transplantation tubulopathies in children: a 9-year experience at a tertiary care centre.

Saudi J Kidney Dis Transpl 2004 Jan-Mar;15(1):27-33

Department of Pediatrics King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

To evaluate the incidence of tubulopathies in the long-term follow-up of children post renal transplantation, we reviewed the records of 43 patients from 1987-1996. There were 24 (56%) boys. The age of patients at the time of transplant ranged from 2.7 to 15 years. Eighteen children (78%) had transplantation from cadaver donors (CAD). Thirty-two (74%) patients were transplanted in Saudi Arabia and 11(26%) were transplanted abroad. Significant tubular dysfunction developed in 72% of patients. Renal Tubular Acidosis (RTA) occurred in 23/43 (53%) patients. The patients who received CAD grafts required higher mean dose of bicarbonate and longer duration of therapy compared to living related donors (LRD) recipients ( mean dose of 1.7 Vs 0.5 meq/kg/day and mean duration of 18 Vs 3 (1/2) months, respectively). Hypophosphatemia of various degrees of severity (0.4-0.8 mmol/1) was detected in 12 (28%) patients. Those who received CAD grafts required higher mean dose of phosphate and longer period of therapy than those who received LRD grafts. Hypomagnesemia requiring supplemental magnesium therapy occurred in 4 (9%) patients, all received tacrolimus therapy. In four patients with hypomagnesemia, this was mild and transient. Hypokalemia was found in 5 (11.5%) patients; all had CAD grafts. We conclude that tubulopathies were a frequent complication post renal transplantation in our population. They were more severe in the patients who received CAD grafts. However, the defects were controllable and transient.
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October 2012