2,659 results match your criteria Alport Syndrome


[Genetic and clinical analysis of a pedigree affected with X-linked dominant Alport syndrome due to a novel variant of COL4A5 gene].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 May;38(5):461-464

Center of Genetic and Prenatal Diagnosis, Department of Gynecology and Obstetrics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.

Objective: To explore the genetic basis for a Chinese pedigree affected with X-linked hereditary Alport syndrome.

Methods: Next generation sequencing was carried out for the pedigree. Candidate variant was validated by Sanger sequencing. Read More

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Autologous retina transplantation for treatment of refractory double full-thickness macular hole in Alport syndrome.

Retin Cases Brief Rep 2021 Jan 13. Epub 2021 Jan 13.

1Department of Ophthalmology, Centro de Oftalmología Barraquer, Barcelona, Spain; 2Instituto Barraquer, Universitat Autònoma de Barcelona, Barcelona, Spain.

Purpose: To report the structural and functional outcomes of autologous neurosensory retinal transplantation for closure of refractory double full-thickness macular hole in a patient diagnosed with Alport syndrome.

Methods: Patient with previous pars plana vitrectomy (PPV) and a failed macular hole surgery (ILM removal) underwent PPV and autologous neurosensory retinal flap transplantation with silicone oil tamponade. Follow-up was performed after one year. Read More

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January 2021

In Vivo Assessment of Metabolic Abnormality in Alport Syndrome Using Hyperpolarized [1-C] Pyruvate MR Spectroscopic Imaging.

Metabolites 2021 Apr 6;11(4). Epub 2021 Apr 6.

Department of Radiology, Chonnam National University Medical School and Hospital, Gwangju 61469, Korea.

Alport Syndrome (AS) is a genetic disorder characterized by impaired kidney function. The development of a noninvasive tool for early diagnosis and monitoring of renal function during disease progression is of clinical importance. Hyperpolarized C MRI is an emerging technique that enables non-invasive, real-time measurement of in vivo metabolism. Read More

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Generation of two induced pluripotent stem cell lines from patients with X-linked Alport syndrome.

Stem Cell Res 2021 Apr 17;53:102343. Epub 2021 Apr 17.

Department of Nephrology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China. Electronic address:

Mutations in COL4A5 on chromosome Xq22 cause X-linked Alport syndrome (XLAS). In this study, we generated two human induced pluripotent stem cell (iPSC) lines from two male patients carrying mutation c.796C > T (p. Read More

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Consensus statement on standards and guidelines for the molecular diagnostics of Alport syndrome: refining the ACMG criteria.

Eur J Hum Genet 2021 Apr 15. Epub 2021 Apr 15.

Medical Genetics Unit, Department of Clinical and Experimental Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.

The recent Chandos House meeting of the Alport Variant Collaborative extended the indications for screening for pathogenic variants in the COL4A5, COL4A3 and COL4A4 genes beyond the classical Alport phenotype (haematuria, renal failure; family history of haematuria or renal failure) to include persistent proteinuria, steroid-resistant nephrotic syndrome, focal and segmental glomerulosclerosis (FSGS), familial IgA glomerulonephritis and end-stage kidney failure without an obvious cause. The meeting refined the ACMG criteria for variant assessment for the Alport genes (COL4A3-5). It identified 'mutational hotspots' (PM1) in the collagen IV α5, α3 and α4 chains including position 1 Glycine residues in the Gly-X-Y repeats in the intermediate collagenous domains; and Cysteine residues in the carboxy non-collagenous domain (PP3). Read More

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Type IV Collagen Variants in CKD: Performance of Computational Predictions for Identifying Pathogenic Variants.

Kidney Med 2021 Mar-Apr;3(2):257-266. Epub 2021 Feb 10.

Division of Nephrology, University Health Network, Toronto, Canada.

Rationale & Objective: Pathogenic variants in type IV collagen have been reported to account for a significant proportion of chronic kidney disease. Accordingly, genetic testing is increasingly used to diagnose kidney diseases, but testing also may reveal rare missense variants that are of uncertain clinical significance. To aid in interpretation, computational prediction (called in silico) programs may be used to predict whether a variant is clinically important. Read More

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February 2021

Genetic Basis of Type IV Collagen Disorders of the Kidney.

Clin J Am Soc Nephrol 2021 Apr 13. Epub 2021 Apr 13.

Division of Pediatric Nephrology, Department of Pediatrics, University of Minnesota Masonic Children's Hospital, Minneapolis, Minnesota

The glomerular basement membrane is a vital component of the filtration barrier of the kidney and is primarily composed of a highly structured matrix of type IV collagen. Specific isoforms of type IV collagen, the 3(IV), 4(IV), and 5(IV) isoforms, assemble into trimers that are required for normal glomerular basement membrane function. Disruption or alteration in these isoforms leads to breakdown of the glomerular basement membrane structure and function and can lead to progressive CKD known as Alport syndrome. Read More

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Could This Be Alport Syndrome?

Clin J Am Soc Nephrol 2021 Apr 13. Epub 2021 Apr 13.

Katz Family Division of Nephrology and Hypertension, University of Miami, Miami, Florida

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Clinical and Genetic Features of Autosomal Dominant Alport Syndrome: A Case Series.

Am J Kidney Dis 2021 Apr 1. Epub 2021 Apr 1.

Inherited Kidney Diseases, Nephrology Department, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Medicine Department-Universitat Autónoma de Barcelona, REDinREN, Instituto de Investigación Carlos III, Barcelona, Spain. Electronic address:

Rationale & Objective: Alport syndrome (AS) is a common genetic kidney disease accounting for approximately 2% of patients receiving kidney replacement therapy (KRT). It is caused by pathogenic variants in COL4A3, COL4A4 or COL4A5 genes. The aim of this study was to evaluate the clinical and genetic spectrum of patients with autosomal dominant Alport syndrome (ADAS). Read More

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A Novel Mutation in LMX1B (p.Pro219Ala) Causes Focal Segmental Glomerulosclerosis with Alport Syndrome-like Phenotype.

Intern Med 2021 Apr 5. Epub 2021 Apr 5.

Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Japan.

A 69-year-old woman presented with mild renal dysfunction, proteinuria, and sensorineural hearing loss. A renal biopsy showed focal segmental glomerulosclerosis with thinning of the glomerular basement membrane. There was a positive family history of end-stage kidney disease and hearing loss. Read More

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Non-Coding RNAs in Hereditary Kidney Disorders.

Int J Mol Sci 2021 Mar 16;22(6). Epub 2021 Mar 16.

Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.

Single-gene defects have been revealed to be the etiologies of many kidney diseases with the recent advances in molecular genetics. Autosomal dominant polycystic kidney disease (ADPKD), as one of the most common inherited kidney diseases, is caused by mutations of PKD1 or PKD2 gene. Due to the complexity of pathophysiology of cyst formation and progression, limited therapeutic options are available. Read More

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Study Design and Baseline Characteristics of the CARDINAL Trial: A Phase 3 Study of Bardoxolone Methyl in Patients with Alport Syndrome.

Am J Nephrol 2021 31;52(3):180-189. Epub 2021 Mar 31.

Renal Associates PA, San Antonio, Texas, USA.

Introduction: Alport syndrome is a rare genetic disorder that affects as many as 60,000 persons in the USA and a total of 103,000 persons (<5 per 10,000) in the European Union [1, 2]. It is the second most common inherited cause of kidney failure and is characterized by progressive loss of kidney function that often leads to end-stage kidney disease. Currently, there are no approved disease-specific agents for therapeutic use. Read More

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Metformin ameliorates the severity of experimental Alport syndrome.

Sci Rep 2021 Mar 29;11(1):7053. Epub 2021 Mar 29.

Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan.

Metformin is widely used for the treatment of type 2 diabetes, and increasing numbers of studies have shown that metformin also ameliorates tumor progression, inflammatory disease, and fibrosis. However, the ability of metformin to improve non-diabetic glomerular disease and chronic kidney disease (CKD) has not been explored. To investigate the effect of metformin on non-diabetic glomerular disease, we used a mouse model of Alport syndrome (Col4a5 G5X) which were treated with metformin or losartan, used as a control treatment. Read More

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Collagen IV dysfunction in glomerular basement membrane diseases. II. Crystal structure of the α345 hexamer.

J Biol Chem 2021 Mar 25:100591. Epub 2021 Mar 25.

Dept. of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN, USA; Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN, USA; Aspirnaut, Vanderbilt University Medical Center, Nashville, TN, USA; Dept. of Pathology, Microbiology and Immunology, Vanderbilt University Med. Center, Nashville, TN, USA; Dept. of Biochemistry, Center for Structural Biology, Vanderbilt University, Nashville, TN, USA; Dept. of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.

Our recent work identified a genetic variant of the α345 hexamer of the collagen IV scaffold that is present in patients with glomerular basement membrane diseases, Goodpasture's disease (GP) and Alport syndrome (AS), and phenocopies AS in knock-in mice (see Companion Paper I). To understand the context of this "Zurich" variant, an 8-amino acid appendage, we developed a construct of the wild-type α345 hexamer using single-chain NC1 trimer technology, which allowed us to solve a crystal structure of this key connection module. The α345 hexamer structure revealed a ring of twelve chloride ions at the trimer-trimer interface, analogous to the collagen α121 hexamer, and the location of the 170 AS variants. Read More

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Collagen IV dysfunction in glomerular basement membrane diseases. III. A functional framework for α345 hexamer assembly.

J Biol Chem 2021 Mar 25:100592. Epub 2021 Mar 25.

Dept. of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN, USA; Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN, USA; Dept. of Biochemistry, Center for Structural Biology, Vanderbilt University, Nashville, TN, USA; Aspirnaut, Vanderbilt University Medical Center, Nashville, TN, USA; Dept. of Pathology, Microbiology and Immunology, Vanderbilt University Med. Center, Nashville, TN, USA; Center for Structural Biology, Vanderbilt University, Nashville, TN, USA; Dept. of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA. Electronic address:

We identified a genetic variant, an 8-residue appendage, of the α345 hexamer of collagen IV present in patients with glomerular basement membrane (GBM) disease, Goodpasture's disease (GP) and Alport syndrome (AS) (see Companion Paper I), and determined the long-awaited crystal structure of hexamer (see Companion Paper II). We sought to elucidate how variants cause GBM disease by exploring the mechanism of hexamer assembly. Chloride ions induced in vitro hexamer assembly in a composition-specific manner in the presence of equimolar concentrations of α3, α4 and α5 NC1 monomers. Read More

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Collagen IV dysfunction in glomerular basement membrane diseases. I. Discovery of a COL4A3 variant in familial Goodpasture's and Alport diseases.

J Biol Chem 2021 Mar 24:100590. Epub 2021 Mar 24.

Dept. of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN, USA; Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN, USA; Aspirnaut Program, Vanderbilt University Medical Center, Nashville, TN; Dept. of Pathology, Microbiology and Immunology, Vanderbilt University Med. Center, Nashville, TN, USA; Dept. of Biochemistry, Vanderbilt University, Nashville, TN, USA; Center for Structural Biology, Vanderbilt University, Nashville, TN, USA; Dept. of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA. Electronic address:

Diseases of the glomerular basement membrane (GBM), such as Goodpasture's disease (GP) and Alport syndrome (AS), are a major cause of chronic kidney failure and an unmet medical need. Collagen IV is an important architectural element of the GBM that was discovered in previous research on GP and AS. How this collagen enables GBM to function as a permselective filter and how structural defects cause renal failure remain an enigma. Read More

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Genotype-phenotype correlations and nephroprotective effects of RAAS inhibition in patients with autosomal recessive Alport syndrome.

Pediatr Nephrol 2021 Mar 27. Epub 2021 Mar 27.

Department of Pediatrics, Peking University First Hospital, No. 1 Xi An Men Da Jie, Beijing, 100034, China.

Background: Autosomal recessive Alport syndrome (ARAS) is caused by pathogenic variants in both alleles of either COL4A3 or COL4A4 genes. Reports on ARAS are rare due to small patient numbers and there are no reports on renin-angiotensin-aldosterone system (RAAS) inhibition therapy in ARAS.

Methods: Retrospective study in 101 patients with ARAS from Chinese Registry Database of Hereditary Kidney Diseases and European Alport Registry. Read More

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Carvedilol and exercise combination therapy improves systolic but not diastolic function and reduces plasma osteopontin in Alport mice.

Am J Physiol Heart Circ Physiol 2021 05 26;320(5):H1862-H1872. Epub 2021 Mar 26.

Interdisciplinary Stem Cell Institute, University of Miami Leonard M. Miller School of Medicine, Miami, Florida.

There are currently no Food and Drug Administration-approved treatments for heart failure with preserved ejection fraction (HFpEF). Here we compared the effects of exercise with and without α/β-adrenergic blockade with carvedilol in Alport mice, a model of the phenogroup 3 subclass of HFpEF with underlying renal dysfunction. Alport mice were assigned to the following groups: no treatment control ( = 29), carvedilol ( = 11), voluntary exercise ( = 9), and combination carvedilol and exercise ( = 8). Read More

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HMGB-1 and TGFβ-1 highlight immuno-inflammatory and fibrotic processes before proteinuria onset in pediatric patients with Alport syndrome.

J Nephrol 2021 Mar 24. Epub 2021 Mar 24.

Nephrology and Dialysis Unit, Papardo Hospital, Messina, Italy.

Introduction: Alport syndrome (ALP) is a rare genetic condition characterized by progressive involvement of the basal membranes and renal dysfunction. The purpose of the study was to evaluate urinary (u) and serum (s) levels of tumor growth factor (TGF)-beta(β) and high mobility group box (HMGB)-1 in ALP patients with normal renal function, albuminuria and proteinuria.

Methods: A prospective, single-center study was performed with a follow-up period of 12 months, enrolling 11 pediatric ALP patients and 10 healthy subjects (HS). Read More

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Kidney-accumulating olmesartan-loaded nanomicelles ameliorate the organ damage in a murine model of Alport syndrome.

Int J Pharm 2021 May 19;600:120497. Epub 2021 Mar 19.

Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea. Electronic address:

ACE inhibitors or angiotensin II receptor blockers (ACEi/ARBs) have been a cornerstone of the management in kidney disease, but their use is often limited by undesired systemic effects, such as symptomatic hypotension. To minimize the extra-renal effects of ACEi/ARBs, we formulated hydrophobically modified glycol chitosan (HGC) nanomicelles releasing olmesartan (HGC-Olm) that specifically accumulated in the kidney, and investigated whether kidney-specific delivery of olmesartan by HGC nanomicelles could ameliorate organ damage in Col4a3 mouse, a murine model of progressive chronic kidney disease mimicking human Alport syndrome. Ex vivo tracing demonstrated that intravenously injected HGC-Olm nanomicelles were specifically delivered to the kidney, with sustained release of olmesartan for more than 48 h. Read More

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Novel Mutations of Identified in Chinese Families with X-Linked Alport Syndrome and Literature Review.

Biomed Res Int 2021 2;2021:6664973. Epub 2021 Mar 2.

Division of Nephrology, Department of Medicine, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, China.

Alport syndrome (AS) is an inherited kidney disease caused by defects in type IV collagen, which is characterized by hematuria, progressive nephritis or end-stage renal disease (ESRD), hearing loss, and occasionally ocular lesions. Approximately 80% of AS cases are caused by X-linked mutations in the gene. This study explored novel deletion and missense mutations in responsible for renal disorder in two Han Chinese families. Read More

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Utility of glomerular Gd-IgA1 staining for indistinguishable cases of IgA nephropathy or Alport syndrome.

Clin Exp Nephrol 2021 Mar 20. Epub 2021 Mar 20.

Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.

Background: Pathological findings in Alport syndrome frequently show mesangial proliferation and sometimes incidental IgA deposition, in addition to unique glomerular basement membrane (GBM) changes including thin basement membrane and/or lamellation. However, similar GBM abnormalities are also often observed in IgA nephropathy. Both diseases are also known to show hematuria, proteinuria, and sometimes macrohematuria when associated with viral infection. Read More

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A glycine substitution in the collagenous domain of Col4a3 in mice recapitulates late onset Alport syndrome.

Matrix Biol Plus 2021 Feb 30;9:100053. Epub 2020 Dec 30.

Center of Excellence in Biobanking and Biomedical Research, Molecular Medicine Research Center, University of Cyprus Medical School, Cyprus.

Alport syndrome (AS) is a severe inherited glomerulopathy caused by mutations in the genes encoding the α-chains of type-IV collagen, the most abundant component of the extracellular glomerular basement membrane (GBM). Currently most AS mouse models are knockout models for one of the collagen-IV genes. In contrast, about half of AS patients have missense mutations, with single aminoacid substitutions of glycine being the most common. Read More

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February 2021

The role of discoidin domain receptor 2 in the renal dysfunction of alport syndrome mouse model.

Ren Fail 2021 Dec;43(1):510-519

Department of Molecular Medicine Graduate School of Pharmaceutical Sciences, Kumamoto, Japan.

Alport syndrome (AS) is a hereditary glomerular nephritis caused by mutation in one of the type IV collagen genes α3/α4/α5 that encode the heterotrimer COL4A3/4/5. Failure to form a heterotrimer due to mutation leads to the dysfunction of the glomerular basement membrane, and end-stage renal disease. Previous reports have suggested the involvement of the receptor tyrosine kinase discoidin domain receptor (DDR) 1 in the progression of AS pathology. Read More

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December 2021

Renal Biopsy-induced Hematoma and Infection in a Patient with Asymptomatic May-Hegglin Anomaly.

J Nippon Med Sch 2021 Mar 9. Epub 2021 Mar 9.

Department of Pediatrics, Graduate School of Medicine, Nippon Medical School.

The May-Hegglin anomaly is characterized by inherited thrombocytopenia, giant platelets, and leukocyte cytoplasmic inclusion bodies. The Fechtner, Sebastian, and Epstein syndromes are associated with mutations of the MYH9-coding nonmuscle myosin heavy chain ⅡA, similar to the May-Hegglin anomaly, and are together classified as MYH9 disorders. MYH9 disorders may include symptoms of Alport syndrome, including nephritis and auditory and ocular disorders. Read More

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Temporal retinal thinning and increased foveal avascular zone blood vessel density in alport syndrome: a case report.

Clin Exp Optom 2021 Feb 27:1-2. Epub 2021 Feb 27.

Advanced Care Ocular Disease Service, Southern College of Optometry, Memphis, TN, USA.

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February 2021

Development of Posterior Lenticonus Following the Diagnosis of Isolated Anterior Lenticonus in Alport Syndrome.

Cureus 2021 Jan 28;13(1):e12970. Epub 2021 Jan 28.

Department of Ophthalmology, Prince Sultan Military Medical City, Riyadh, SAU.

Alport syndrome is a genetic disorder that manifests as renal disease, hearing loss and ocular dysfunction. Lenticonus is one such ocular condition, in which the lens takes on an abnormal cone shape, with a protrusion either at the front or back of the lens. Both sides of the lens are rarely affected at the same time in the general patient population. Read More

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January 2021

Population-based studies reveal an additive role of type IV collagen variants in hematuria and albuminuria.

Pediatr Nephrol 2021 Feb 26. Epub 2021 Feb 26.

Institute of Medical Sciences, University of Toronto, Toronto, Canada.

Specific variants in genes that encode the α3α4α5 chains of type IV collagen cause Alport syndrome (AS), which encompass a clinical spectrum from isolated hematuria to multisystem disease affecting sight, hearing and kidney function. The commonest form is X-linked Alport syndrome (XLAS; COL4A5) with autosomal AS (COL4A3 and COL4A4) comprising a minority of cases. While historic data estimates the frequency of AS at 1:5000-10,000, recent population-based genetic studies suggest the prevalence is considerably higher. Read More

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February 2021

Case Report: Preimplantation Genetic Testing and Pregnancy Outcomes in Women With Alport Syndrome.

Front Genet 2021 9;12:633003. Epub 2021 Feb 9.

International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Alport syndrome, a monogenic kidney disease, is characterized by progressive hemorrhagic nephritis, sensorineural hearing loss, and ocular abnormalities. Mutations in at Xq22 accounts for 80-85% of X-linked Alport syndrome patients. Three couples were referred to our reproductive genetics clinic for prenatal or preconception counseling. Read More

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February 2021

Corneal cross-linking for treatment of progressive keratoconus in a patient with Alport syndrome: A case report.

Eur J Ophthalmol 2021 Feb 25:1120672121997672. Epub 2021 Feb 25.

School of Medicine, University of Zagreb, Zagreb, Croatia.

Purpose: Ocular features of Alport syndrome include anterior lenticonus, posterior polymorphous corneal dystrophy, and fleck-and-dot retinopathy in most cases. Keratoconus in such patients has been rarely mentioned in previous studies. To our knowledge, this is the first report of corneal cross-linking for halting the progression of keratoconus in a patient with Alport syndrome. Read More

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February 2021