Novel missense mutations of TMPRSS3 in two consanguineous Tunisian families with non-syndromic autosomal recessive deafness

Autor: 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
Přispěvatelé: 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, Ciccodicola, Alfredo
Rok vydání: 2001
Předmět:
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
Zdroj: Human Mutation, Vol. 18, No 2 (2001) pp. 101-108
ISSN: 1098-1004
1059-7794
Popis: 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.
Databáze: OpenAIRE
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