A Novel Mutation in a Kazakh Family with X-Linked Alport Syndrome.

Barshagul T Baikara,Kuvat T Momynaliev,Nazym B Nigmatullina,Yerlan M Ramanculov,Elena V Zholdybayeva,Saule E Rakhimova,Gyaneshwer Chaubey

doi:10.1371/journal.pone.0132010

Abstract

Alport syndrome is a genetic condition that results in hematuria, progressive renal impairment, hearing loss, and occasionally lenticonus and retinopathy. Approximately 80% of Alport syndrome cases are caused by X-linked mutations in the COL4A5 gene encoding type IV collagen. The objective of this study was to define the SNP profiles for COL4A5 in patients with hereditary nephritis and hematuria. For this, we examined four subjects from one Kazakh family clinically affected with X-linked Alport syndrome due to COL4A5 gene mutations. All 51 exons of the COL4A5 gene were screened by linkage analysis and direct DNA sequencing, resulting in the identification of a novel mutation (G641E) in exon 25. The mutation was found only in two affected family individuals but was not present in healthy family members or 200 unrelated healthy controls. This result demonstrates that this novel mutation is pathogenic and has meaningful implications for the diagnosis of patients with Alport syndrome.

Highlights

In 1927, Alport reported that deafness was a feature of a previously described familial nephropathy that caused uremia in males [1]
Subsequent studies found that this renal dysfunction results from splitting of the glomerular basement membrane (GBM), hematuria, interstitial nephritis, and progressive kidney failure [2]; the genetic basis for Alport syndrome was unknown until mutations in the COL4A3, COL4A4, and COL4A5 collagen genes were discovered in clinically affected families [3,4,5,6]
We investigated a Kazakh family with Alport syndrome

Summary

Introduction

In 1927, Alport reported that deafness was a feature of a previously described familial nephropathy that caused uremia in males [1]. Subsequent studies found that this renal dysfunction results from splitting of the glomerular basement membrane (GBM), hematuria, interstitial nephritis, and progressive kidney failure [2]; the genetic basis for Alport syndrome was unknown until mutations in the COL4A3, COL4A4, and COL4A5 collagen genes were discovered in clinically affected families [3,4,5,6]. Alport syndrome is an inherited disease characterized by hematuria and/or proteinuria, and occasionally sensorineural hearing loss and eye lesions, which progresses to chronic renal failure [8]. Alport syndrome is a genetically heterogeneous disease; the pathogenesis of X-linked Alport syndrome is attributed to mutations in one of the three genes encoding type.

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Conclusion