Targeted exome sequencing reveals novel USH2A mutations in Chinese patients with simplex Usher syndromeReportar como inadecuado




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BMC Medical Genetics

, 16:83

First Online: 16 September 2015Received: 27 December 2014Accepted: 21 August 2015

Abstract

BackgroundUsher syndrome USH is an autosomal recessive disorder characterized by hearing impairment and vision dysfunction due to retinitis pigmentosa. Phenotypic and genetic heterogeneities of this disease make it impractical to obtain a genetic diagnosis by conventional Sanger sequencing.

MethodsIn this study, we applied a next-generation sequencing approach to detect genetic abnormalities in patients with USH. Two unrelated Chinese families were recruited, consisting of two USH afflicted patients and four unaffected relatives. We selected 199 genes related to inherited retinal diseases as targets for deep exome sequencing. Through systematic data analysis using an established bioinformatics pipeline, all variants that passed filter criteria were validated by Sanger sequencing and co-segregation analysis.

ResultsA homozygous frameshift mutation c.4382delA, p.T1462Lfs*2 was revealed in exon20 of gene USH2A in the F1 family. Two compound heterozygous mutations, IVS47 + 1G > A and c.13156A > T p.I4386F, located in intron 48 and exon 63 respectively, of USH2A, were identified as causative mutations for the F2 family. Of note, the missense mutation c.13156A > T has not been reported so far.

ConclusionIn conclusion, targeted exome sequencing precisely and rapidly identified the genetic defects in two Chinese USH families and this technique can be applied as a routine examination for these disorders with significant clinical and genetic heterogeneity.

AbbreviationsUSHUsher syndrome

SNVsSingle-nucleotide variants

IndelsInsertions or deletions

OCTOptical coherence tomography

PCRPolymerase chain reaction

NGSNext-generation sequencing

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Autor: Hai-Rong Shu - Huai Bi - Yang-Chun Pan - Hang-Yu Xu - Jian-Xin Song - Jie Hu

Fuente: https://link.springer.com/







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