Dataset Information

GPRASP2, a novel causative gene mutated in an X-linked recessive syndromic hearing loss.

ABSTRACT: BACKGROUND:A substantial amount of nuclear genes have been identified to be implicated in genetic hearing loss, while X-linked hearing loss is genetically heterogeneous and relatively infrequent. OBJECTIVE:To identify the causative gene mutation in a five-generation Chinese family with an X-linked recessive syndromic hearing loss (SHL). METHODS:Targeted X-chromosome exome sequencing was conducted, and cosegregation analysis was performed in the members of the affected family. The in silico and expression studies were also performed. RESULTS:A 2-bp missense mutation (c.1717_1718GC>AA, p.A573N) in the G protein-coupled receptor associated sorting protein 2 (GPRASP2) gene was identified in four hemizygous male patients and two heterozygous female carriers, which was cosegregated with the clinical phenotypes in this family. In silico analysis supported that this gene mutation is functionally deleterious, and it was detected that homologous Gprasp2 was highly expressed in multiple structures of the mouse cochlea, which suggested that GPRASP2 might be the genetic cause for the described disease phenotypes. CONCLUSIONS:This study presented a novel X-linked SHL combined with unique and unrecognised clinical features, and a missense variation of GPRASP2 was first identified to be implicated in X-linked SHL.

SUBMITTER: Xing G

PROVIDER: S-EPMC5502311 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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<i>GPRASP2</i>, a novel causative gene mutated in an X-linked recessive syndromic hearing loss.

Xing Guangqian G Yao Jun J Liu Chunyu C Wei Qinjun Q Qian Xuli X Wu Lingxin L Lu Yajie Y Cao Xin X

Journal of medical genetics 20170117 6

<h4>Background</h4>A substantial amount of nuclear genes have been identified to be implicated in genetic hearing loss, while X-linked hearing loss is genetically heterogeneous and relatively infrequent.<h4>Objective</h4>To identify the causative gene mutation in a five-generation Chinese family with an X-linked recessive syndromic hearing loss (SHL).<h4>Methods</h4>Targeted X-chromosome exome sequencing was conducted, and cosegregation analysis was performed in the members of the affected famil ...[more]

PMID: 28096187

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Project description:The frequency of inherited bilateral autosomal recessive non-syndromic hearing loss (ARNSHL) in Pakistan is 1.6/1000 individuals. More than 50% of the families carry mutations in GJB2 while mutations in MYO15A account for about 5% of recessive deafness. In the present study a cohort of 30 ARNSHL families was initially screened for mutations in GJB2 and MYO15A. Homozygosity mapping was performed by employing whole genome single nucleotide polymorphism (SNP) genotyping in the families that did not carry mutations in GJB2 or MYO15A. Mutation analysis was performed for the known ARNSHL genes present in the homozygous regions to determine the causative mutations. This allowed the identification of a causative mutation in all the 30 families including 9 novel mutations, which were identified in 9 different families (GJB2 (c.598G>A, p.Gly200Arg); MYO15A (c.9948G>A, p.Gln3316Gln; c.3866+1G>A; c.8767C>T, p.Arg2923* and c.8222T>C, p.Phe2741Ser), TMC1 (c.362+18A>G), BSND (c.97G>C, p.Val33Leu), TMPRSS3 (c.726C>G, p.Cys242Trp) and MSRB3 (c.20T>G, p.Leu7Arg)). Furthermore, 12 recurrent mutations were detected in 21 other families. The 21 identified mutations included 10 (48%) missense changes, 4 (19%) nonsense mutations, 3 (14%) intronic mutations, 2 (9%) splice site mutations and 2 (9%) frameshift mutations. GJB2 accounted for 53% of the families, while mutations in MYO15A were the second most frequent (13%) cause of ARNSHL in these 30 families. The identification of novel as well as recurrent mutations in the present study increases the spectrum of mutations in known deafness genes which could lead to the identification of novel founder mutations and population specific mutated deafness genes causative of ARNSHL. These results provide detailed genetic information that has potential diagnostic implication in the establishment of cost-efficient allele-specific analysis of frequently occurring variants in combination with other reported mutations in Pakistani populations.

Dataset Information

GPRASP2, a novel causative gene mutated in an X-linked recessive syndromic hearing loss.

Publications

<i>GPRASP2</i>, a novel causative gene mutated in an X-linked recessive syndromic hearing loss.

Similar Datasets

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