title: Novel Mutations and Mutation Combinations ofTMPRSS3Cause Various Phenotypes in One Chinese Family with Autosomal Recessive Hearing Impairment.
abstract: Autosomal recessive hearing impairment with postlingual onset is rare. Exceptions are caused by mutations in theTMPRSS3gene, which can lead to prelingual (DFNB10) as well as postlingual deafness (DFNB8).TMPRSS3mutations can be classified as mild or severe, and the phenotype is dependent on the combination ofTMPRSS3mutations. The combination of two severe mutations leads to profound hearing impairment with a prelingual onset, whereas severe mutations in combination with milderTMPRSS3mutations lead to a milder phenotype with postlingual onset. We characterized a Chinese family (number FH1523) with not only prelingual but also postlingual hearing impairment. Three mutations inTMPRSS3, one novel mutation c.36delC [p.(Phe13Serfs⁎12)], and two previously reported pathogenic mutations, c.916G>A (p.Ala306Thr) and c.316C>T (p.Arg106Cys), were identified. Compound heterozygous mutations of p.(Phe13Serfs⁎12) and p.Ala306Thr manifest as prelingual, profound hearing impairment in the patient (IV: 1), whereas the combination of p.Arg106Cys and p.Ala306Thr manifests as postlingual, milder hearing impairment in the patient (II: 2, II: 3, II: 5), suggesting that p.Arg106Cys mutation has a milder effect than p.(Phe13Serfs⁎12). We concluded that different combinations ofTMPRSS3mutations led to different hearing impairment phenotypes (DFNB8/DFNB10) in this family.
authors.affiliation: Department of Otolaryngology, The General Hospital of the PLA Rocket Force, No. 16 Xinwai Dajie, Beijing 100088, China.
authors.forename: Xue
authors.identifier: 0000-0003-4305-1206
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, China.
authors.forename: Yong-Yi
authors.identifier: 0000-0002-7936-4776
authors.initials: YY
authors.lastname: Yuan
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, China.
authors.forename: Guo-Jian
authors.initials: GJ
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, The General Hospital of the PLA Rocket Force, No. 16 Xinwai Dajie, Beijing 100088, China.
authors.forename: Jin-Cao
authors.initials: JC
authors.lastname: Xu
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Otolaryngology, Emory University School of Medicine, 615 Michael Street, Whitehead Biomedical Research Bldg, Rm No. 543, Atlanta, GA 30322, USA.
authors.forename: Xi
authors.identifier: 0000-0002-1345-8374
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, China.
authors.forename: Pu
authors.identifier: 0000-0003-0718-8889
authors.initials: P
authors.lastname: Dai
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001299:Audiometry; D001483:Base Sequence; D002648:Child; D003054:Cochlear Implants; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics; D005190:Family; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D034381:Hearing Loss / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012697:Serine Endopeptidases / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D050505:Mutant Proteins; D009363:Neoplasm Proteins; D012697:Serine Endopeptidases; C409042:TMPRSS3 protein, human