Clinical and genetic analysis of two Tunisian otosclerosis families.
Otosclerosis is caused by an abnormal bone homeostasis of the otic capsule resulting in a conductive hearing loss when the free motion of the stapes is compromised. An additional sensorineural hearing loss arises in some patients, most likely due to otosclerotic foci that invade the cochlear endosteum. Otosclerosis is a very common hearing impairment among Caucasians with a prevalence of about 0.3-0.4% among white adults. In the majority of cases, otosclerosis can be considered as a complex disease, caused by both genetic as environmental factors, but autosomal dominant forms of otosclerosis exist. However, families large enough for genetic analysis are very rare and often show reduced penetrance. To date five loci have been reported, but none of the genes have been cloned yet. In this study, we analyzed two new autosomal dominant otosclerosis families from Tunisia, and genotyped them with microsatellite markers for the known loci, the collagen genes COL1A1 and COL1A2, and NOG gene. In the family LK, linkage to all known loci was excluded. However, the family LS shows suggestive linkage to the OTSC3 region on chromosome 6p21.3-p22.3. This result points out that, besides the five reported loci, there must be at least one additional locus for autosomal dominant otosclerosis.
Ali
Insaf Bel Hadj
IB
Unité d'Epidémiologie Génétique et Moléculaire-Faculté de Médecine de Tunis, Tunisia.
Thys
Melissa
M
Beltaief
Najeh
N
Schrauwen
Isabelle
I
Dieltjens
Nele
N
Vanderstraeten
Kathleen
K
Besbes
Ghazi
G
Mnif
Emna
E
Hachicha
Slah
S
Arab
Saïda Ben
SB
Camp
Guy Van
GV
D000293:Adolescent; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D003094:Collagen / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010040:Otosclerosis / Q000235:genetics* / Q000473:pathology*; D010375:Pedigree; D014416:Tunisia; D000099176:Noggin Protein
D002352:Carrier Proteins; D003094:Collagen; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D000099176:Noggin Protein