title: Deafness heterogeneity in a Druze isolate from the Middle East: novel OTOF and PDS mutations, low prevalence of GJB2 35delG mutation and indication for a new DFNB locus.
abstract: About 60% of congenital hearing impairment cases in developed countries are due to genetic defects. Data on the molecular basis of hereditary hearing reflects vast genetic heterogeneity. There are >400 disorders in which hearing impairment is one of the characteristic traits of a syndrome. Linkage studies have identified more than 40 human chromosomal loci associated with non-syndromic hearing loss. So far, 16 of these 40 non-syndromic hearing impairment genes have been identified. We have studied the molecular basis of hearing impairment in four Druze families from the same village in Northern Galilee. The Druze are a small, isolated population in the Middle East practising endogamous marriage. Thus it was expected that a single mutation would account for hearing impairments in all these families. Our results show that at least four different genes are involved. Hearing impairment was caused in one family by a novel mutation in the recently identified OTOF (the DFNB9 gene), by a novel Pendred syndrome mutation (Thr193Ile) in another family, and by a GJB2 mutation (35delG also known as 30delG) in the third family. In the fourth family linkage was excluded from all known hearing impairments loci (recessive and dominant) as well as from markers covering chromosomes 11-22, pointing therefore to the existence of another non-syndromic recessive hearing loss (NSRD) locus on chromosomes 1-10.
authors.affiliation: Department of Human Genetics, Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Adato
authors.forename: L
authors.initials: L
authors.lastname: Raskin
authors.forename: C
authors.initials: C
authors.lastname: Petit
authors.forename: B
authors.initials: B
authors.lastname: Bonne-Tamir
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D000072259:Connexin 26; D017630:Connexins; D003241:Consanguinity; D004252:DNA Mutational Analysis; D003638:Deafness / Q000151:congenital / Q000208:ethnology / Q000235:genetics*; D005260:Female; D006042:Goiter / Q000235:genetics; D006801:Humans; D007557:Israel; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D000076988:Sulfate Transporters; D013577:Syndrome
chemical_list: D002352:Carrier Proteins; D017630:Connexins; C000607042:GJB2 protein, human; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C118457:OTOF protein, human; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26