title: TMPRSS3, a type II transmembrane serine protease mutated in non-syndromic autosomal recessive deafness.
abstract: Recently, we and others have shown that mutations in TMPRSS3 were responsible for autosomal recessive non-syndromic hearing loss. TMPRSS3 is a member of the Type II Transmembrane Serine Protease (TTSP) family and encodes for a protease that also contains LDLRA (low-density lipoprotein receptor class A) and SRCR (scavenger receptor cysteine rich) domains. Fourteen pathogenic mutations, which occur not only in the catalytic domain but also in the LDLRA and SRCR domains, have been identified to date that cause the DFNB8/10 forms of deafness. In vitro experiments demonstrated that TMPRSS3 mutants were proteolytically inactive indicating that TMPRSS3 protease activity is critical for normal auditory function. However, how missense mutations in the LDLRA and SRCR domains affect the proteolytic activity of TMPRSS3 remains to be elucidated. Although the role of TMPRSS3 in the auditory system is currently not completely understood, it has been shown to regulate the activity of the ENaC sodium channel in vitro and could therefore participate in the regulation of sodium concentration in the cochlea. TMPRSS3 mutations are not a common cause of hereditary deafness, the elucidation of its function is nevertheless important for better understanding of hearing, and provide biological targets for therapeutic interventions.
authors.affiliation: Division of Medical Genetics, University Hospital of Geneva, Geneva, Switzerland. Michel.Guipponi@hcuge.ch
authors.forename: Michel
authors.initials: M
authors.lastname: Guipponi
authors.forename: Stylianos Emmanuel
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: Hamish Steele
authors.initials: HS
authors.lastname: Scott
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005808:Genes, Recessive; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012697:Serine Endopeptidases; C409042:TMPRSS3 protein, human