Dataset Information

Identification of novel USH2A mutations in patients with autosomal recessive retinitis pigmentosa via targeted next?generation sequencing.

ABSTRACT: Retinitis pigmentosa (RP) is a group of inheritable blindness retinal diseases characterized by the death of photoreceptor cells and a gradual loss of peripheral vision. Mutations in Usher syndrome type 2 (USH2A) have been reported in RP with or without hearing loss. The present study aimed to identify causative mutations in a cohort of families with RP from China. A cohort of 62 non?syndromic families with RP and 30 sporadic cases were enrolled in this study. All affected members underwent a complete ophthalmic examination, including fundus photography, visual?field test and optical coherence tomography examination. Next?generation sequencing?targeted sequencing of 163 genes involved in inheritable retinal disorders was performed on the probands. Stringent bioinformatics data analysis was applied to identify potential candidate variants. In total, 6 novel mutations and 2 known mutations of USH2A were identified in 4 families with RP. A stop?gain mutation (c.C1731A) and a missense mutation (c.G8254A) were identified in RP family RP?2148. In another RP family, RP?2150, a known mutation (c.G802A) and a novel frameshift insertion mutation (c.12086dupA) were discovered. A novel stop?gain mutation (c.G11754A) and a missense mutation (c.G13465A) were identified in family rpz05. A novel missense mutation (c.C9328G) and a known missense mutation (c.G8232C) were also identified. These mutations were subsequently confirmed by Sanger sequencing. All 6 novel mutations affected highly conserved amino acid residues, and were absent in 1,000 ethnically matched controls. Taken together, the present study has reported on 6 novel USH2A mutations in 4 families with RP, and has expanded the mutation spectrum of USH2A in autosomal recessive RP in the Chinese population, thus providing important information for the molecular diagnosis and screening of RP.

SUBMITTER: Zhu X

PROVIDER: S-EPMC7248525 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of novel USH2A mutations in patients with autosomal recessive retinitis pigmentosa via targeted next‑generation sequencing.

Zhu Xiong X Li Xiao X Tian Wanli W Yang Yeming Y Sun Kuanxiang K Li Shuzhen S Zhu Xianjun X

Molecular medicine reports 20200422 1

Retinitis pigmentosa (RP) is a group of inheritable blindness retinal diseases characterized by the death of photoreceptor cells and a gradual loss of peripheral vision. Mutations in Usher syndrome type 2 (USH2A) have been reported in RP with or without hearing loss. The present study aimed to identify causative mutations in a cohort of families with RP from China. A cohort of 62 non‑syndromic families with RP and 30 sporadic cases were enrolled in this study. All affected members underwent a co ...[more]

PMID: 32319668

Similar Datasets

Project description:PURPOSE: Retinitis pigmentosa (RP) is an inherited retinal dystrophy characterized by extreme genetic and clinical heterogeneity. Thus, the diagnosis is not always easily performed due to phenotypic and genetic overlap. Current clinical practices have focused on the systematic evaluation of a set of known genes for each phenotype, but this approach may fail in patients with inaccurate diagnosis or infrequent genetic cause. In the present study, we investigated the genetic cause of autosomal recessive RP (arRP) in a Spanish family in which the causal mutation has not yet been identified with primer extension technology and resequencing. METHODS: We designed a whole-exome sequencing (WES)-based approach using NimbleGen SeqCap EZ Exome V3 sample preparation kit and the SOLiD 5500×l next-generation sequencing platform. We sequenced the exomes of both unaffected parents and two affected siblings. Exome analysis resulted in the identification of 43,204 variants in the index patient. All variants passing filter criteria were validated with Sanger sequencing to confirm familial segregation and absence in the control population. In silico prediction tools were used to determine mutational impact on protein function and the structure of the identified variants. RESULTS: Novel Usher syndrome type 2A (USH2A) compound heterozygous mutations, c.4325T>C (p.F1442S) and c.15188T>G (p.L5063R), located in exons 20 and 70, respectively, were identified as probable causative mutations for RP in this family. Family segregation of the variants showed the presence of both mutations in all affected members and in two siblings who were apparently asymptomatic at the time of family ascertainment. Clinical reassessment confirmed the diagnosis of RP in these patients. CONCLUSIONS: Using WES, we identified two heterozygous novel mutations in USH2A as the most likely disease-causing variants in a Spanish family diagnosed with arRP in which the cause of the disease had not yet been identified with commonly used techniques. Our data reinforce the clinical role of WES in the molecular diagnosis of highly heterogeneous genetic diseases where conventional genetic approaches have previously failed in achieving a proper diagnosis.

Dataset Information

Identification of novel USH2A mutations in patients with autosomal recessive retinitis pigmentosa via targeted next?generation sequencing.

Publications

Identification of novel USH2A mutations in patients with autosomal recessive retinitis pigmentosa via targeted next‑generation sequencing.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets