Dataset Information

Identification of a novel homozygous mutation, TMPRSS3: c.535G>A, in a Tibetan family with autosomal recessive non-syndromic hearing loss.

ABSTRACT: Different ethnic groups have distinct mutation spectrums associated with inheritable deafness. In order to identify the mutations responsible for congenital hearing loss in the Tibetan population, mutation screening for 98 deafness-related genes by microarray and massively parallel sequencing of captured target exons was conducted in one Tibetan family with familiar hearing loss. A homozygous mutation, TMPRSS3: c.535G>A, was identified in two affected brothers. Both parents are heterozygotes and an unaffected sister carries wild type alleles. The same mutation was not detected in 101 control Tibetan individuals. This missense mutation results in an amino acid change (p.Ala179Thr) at a highly conserved site in the scavenger receptor cysteine rich (SRCR) domain of the TMPRSS3 protein, which is essential for protein-protein interactions. Thus, this mutation likely affects the interactions of this transmembrane protein with extracellular molecules. According to our bioinformatic analyses, the TMPRSS3: c.535G>A mutation might damage protein function and lead to hearing loss. These data suggest that the homozygous mutation TMPRSS3: c.535G>A causes prelingual hearing loss in this Tibetan family. This is the first TMPRSS3 mutation found in the Chinese Tibetan population.

SUBMITTER: Fan D

PROVIDER: S-EPMC4256404 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Identification of a novel homozygous mutation, TMPRSS3: c.535G>A, in a Tibetan family with autosomal recessive non-syndromic hearing loss.

Fan Dongyan D Zhu Wei W Li Dejun D Ji De D Wang Ping P

PloS one 20141204 12

Different ethnic groups have distinct mutation spectrums associated with inheritable deafness. In order to identify the mutations responsible for congenital hearing loss in the Tibetan population, mutation screening for 98 deafness-related genes by microarray and massively parallel sequencing of captured target exons was conducted in one Tibetan family with familiar hearing loss. A homozygous mutation, TMPRSS3: c.535G>A, was identified in two affected brothers. Both parents are heterozygotes and ...[more]

PMID: 25474651

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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

Identification of a novel homozygous mutation, TMPRSS3: c.535G>A, in a Tibetan family with autosomal recessive non-syndromic hearing loss.

Publications

Identification of a novel homozygous mutation, TMPRSS3: c.535G>A, in a Tibetan family with autosomal recessive non-syndromic hearing loss.

Similar Datasets

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