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BMC Med Genet. 2015 Sep 16;16:83. doi: 10.1186/s12881-015-0223-9.

Targeted exome sequencing reveals novel USH2A mutations in Chinese patients with simplex Usher syndrome.

Author information

1
Department of Otolaryngology, Taizhou Central Hospital, Taizhou University School of Medicine, No 999, Donghai Rd., Taizhou, Zhejiang, 318000, China. drshu@126.com.
2
Department of Otolaryngology, Taihe People's Hospital, No 158, Shengli Rd., Taihe, Jiangxi, 343700, China.
3
Department of Otolaryngology, the Forth Affiliated Hospital of Shihezi University School of Medicine, Beier Rd., Shihezi, Xinjiang, 843000, China.
4
Department of Otolaryngology, Taizhou Central Hospital, Taizhou University School of Medicine, No 999, Donghai Rd., Taizhou, Zhejiang, 318000, China.
5
Department of Ophthalmology, Taizhou Central Hospital, Taizhou University School of Medicine, No 999, Donghai Rd., Taizhou, Zhejiang, 318000, China. hujietaizhou@163.com.

Abstract

BACKGROUND:

Usher 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.

METHODS:

In 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.

RESULTS:

A 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.

CONCLUSION:

In 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.

PMID:
26377068
PMCID:
PMC4571113
DOI:
10.1186/s12881-015-0223-9
[Indexed for MEDLINE]
Free PMC Article

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