A novel TMPRSS3 missense mutation in a DFNB8/10 family prevents proteolytic activation of the protein.

Détails

ID Serval
serval:BIB_FFEE7EE86CAA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A novel TMPRSS3 missense mutation in a DFNB8/10 family prevents proteolytic activation of the protein.
Périodique
Human Genetics
Auteur⸱e⸱s
Wattenhofer M., Sahin-Calapoglu N., Andreasen D., Kalay E., Caylan R., Braillard B., Fowler-Jaeger N., Reymond A., Rossier B.C., Karaguzel A., Antonarakis S.E.
ISSN
0340-6717[print], 0340-6717[linking]
Statut éditorial
Publié
Date de publication
2005
Peer-reviewed
Oui
Volume
117
Numéro
6
Pages
528-535
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Pathogenic mutations in TMPRSS3, which encodes a transmembrane serine protease, cause non-syndromic deafness DFNB8/10. Missense mutations map in the low density-lipoprotein receptor A (LDLRA), scavenger-receptor cysteine-rich (SRCR), and protease domains of the protein, indicating that all domains are important for its function. TMPRSS3 undergoes proteolytic cleavage and activates the ENaC sodium channel in a Xenopus oocyte model system. To assess the importance of this gene in non-syndromic childhood or congenital deafness in Turkey, we screened for mutations affected members of 25 unrelated Turkish families. The three families with the highest LOD score for linkage to chromosome 21q22.3 were shown to harbor P404L, R216L, or Q398X mutations, suggesting that mutations in TMPRSS3 are a considerable contributor to non-syndromic deafness in the Turkish population. The mutant TMPRSS3 harboring the novel R216L missense mutation within the predicted cleavage site of the protein fails to undergo proteolytic cleavage and is unable to activate ENaC, thus providing evidence that pre-cleavage of TMPRSS3 is mandatory for normal function.
Mots-clé
Amino Acid Sequence, Chromosomes, Human, Pair 21, Deafness/genetics, Female, Haplotypes, Humans, Linkage (Genetics), Lod Score, Male, Membrane Proteins/genetics, Membrane Proteins/metabolism, Molecular Sequence Data, Mutation, Missense, Neoplasm Proteins/genetics, Neoplasm Proteins/metabolism, Pedigree, Serine Endopeptidases/genetics, Serine Endopeptidases/metabolism
Pubmed
Web of science
Création de la notice
24/01/2008 13:00
Dernière modification de la notice
20/08/2019 16:30
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