1. Novel missense mutations of TMPRSS3 in two consanguineous Tunisian families with non-syndromic autosomal recessive deafness
- Author
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Miano, Maria Giuseppina, Filippini, Francesco, Trujillo, Mariajos, Conte, Ivan, Lanzara, Carmela, Milln, Jos Maria, De Bernardo, Carmelilia, Grammatico, Barbara, Mangino, Massimo, Torrente, Isabella, Carrozzo, Romeo, Rinaldi, Ernesto, Ventruto, Valerio, Durso, Michele, Ayuso, Carmen, Ciccodicola, Alfredo, TESTA, Francesco, SIMONELLI, Francesca, Miano, Maria Giuseppina, Testa, Francesco, Filippini, Francesco, Trujillo, Mariajo, Conte, Ivan, Lanzara, Carmela, Milln, Jos Maria, De Bernardo, Carmelilia, Grammatico, Barbara, Mangino, Massimo, Torrente, Isabella, Carrozzo, Romeo, Simonelli, Francesca, Rinaldi, Ernesto, Ventruto, Valerio, Durso, Michele, Ayuso, Carmen, and Ciccodicola, Alfredo
- Subjects
Comparative protein modeling ,Male ,Models, Molecular ,DFNB10 ,Chromosomes, Human, Pair 21 ,Genetic Linkage ,medicine.medical_treatment ,DNA Mutational Analysis ,Conserved sequence ,Protease, serine ,Consanguinity ,Genes, Recessive/genetics ,Serine Endopeptidases/chemistry/ genetics ,Missense mutation ,Membrane Protein ,Genetics (clinical) ,Conserved Sequence ,ddc:616 ,Genetics ,biology ,Linkage ,Mutation analysi ,Serine Endopeptidases ,Chromosomes, Human, Pair 21/genetics ,Chromosome Mapping ,Neoplasm Proteins ,Pedigree ,Serine protease ,Serine Endopeptidase ,Mutation (genetic algorithm) ,Female ,Conserved Sequence/genetics ,Human ,Tunisia ,Genotype ,Mutation, Missense/ genetics ,Hearing Loss, Sensorineural ,Molecular Sequence Data ,Hearing Loss, Sensorineural/congenital/ genetics ,Mutation, Missense ,Locus (genetics) ,Genes, Recessive ,DNA Mutational Analysi ,Neoplasm Protein ,Genetic ,Audiometry ,Genetic linkage ,DFNB8 ,Linkage (Genetics)/genetics ,medicine ,Humans ,Amino Acid Sequence ,Deafne ,Gene ,TMPRSS3 ,Protease ,Binding Sites ,Base Sequence ,Binding Site ,Membrane Proteins ,Molecular biology ,Protein Structure, Tertiary ,biology.protein ,Transmembrane protease, serine, 3 ,Non syndromic - Abstract
Recently the TMPRSS3 gene, which encodes a transmembrane serine protease, was found to be responsible for two non-syndromic recessive deafness loci located on human chromosome 21q22.3, DFNB8 and DFNB10. We found evidence for linkage to the DFNB8/10 locus in two unrelated consanguineous Tunisian families segregating congenital autosomal recessive sensorineural deafness. The audiometric tests showed a loss of hearing greater than 70 dB, in all affected individuals of both families. Mutation screening of TMPRSS3 revealed two novel missense mutations, W251C and P404L, altering highly conserved amino acids of the serine protease domain. Both mutations were not found in 200 control Tunisian chromosomes. The detection of naturally-occurring TMPRSS3 missense mutations in deafness families identifies functionally important amino acids. Comparative protein modeling of the TMPRSS3 protease domain predicted that W251C might lead to a structural rearrangement affecting the active site H257 and that P404L might alter the geometry of the active site loop and therefore affect the serine protease activity.
- Published
- 2001