title: 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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, the First Hospital of Jilin University, Changchun, Jilin Province, China; Tibet University School of Medicine, Lhasa, China.
authors.forename: Dongyan
authors.initials: D
authors.lastname: Fan
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, the First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Center for Prenatal Diagnosis, the First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Dejun
authors.initials: D
authors.lastname: Li
authors.affiliation: Tibet University School of Medicine, Lhasa, China.
authors.forename: De
authors.initials: D
authors.lastname: Ji
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, the First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D044466:Asian People / Q000235:genetics*; D001298:Audiology; D002648:Child; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D034381:Hearing Loss / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D011379:Prognosis; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics*; D035781:Siblings; D018609:Tibet
chemical_list: D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012697:Serine Endopeptidases; C409042:TMPRSS3 protein, human