A founder TMIE mutation is a frequent cause of hearing loss in southeastern Anatolia.
Using Affymetrix 10K arrays, we searched for regions of homozygosity in 51 Turkish families including at least three members with either congenital or prelingual autosomal recessive non-syndromic sensorineural hearing loss (ARNSSNHL), and identified four families whose deafness mapped to the DFNB6 locus on 3p21 containing the TMIE gene. Mutation analysis revealed the p.R84W mutation in all four families. Screening of this mutation in 254 families with ARNSSNHL, without GJB2 mutations, revealed four additional affected families. A novel mutation was found in a non-complementary marriage between a deaf couple who were homozygous for p.R84W and p.W57X, respectively with two affected children who were compound heterozygotes. Six of the TMIE families originated from southeastern Anatolia, making p.R84W a common cause of hearing loss in that region with a relative frequency of 10.3% (95% CI is 2.5-18.1%). The overall prevalence of the p.R84W mutation in ARNSSNHL in Turkey is 2.4% (95% CI is 0.7-4.0%). Genotyping of single-nucleotide polymorphisms flanking the TMIE gene revealed a conserved haplotype, suggesting a single origin for p.R84W from a common ancestor 1250 years ago (95% CI is 650-2500 years). We conclude that p.R84W could be a common mutation in other Middle Eastern populations and should be included in mutation screening offered to individuals with ARNSSNHL.
Division of Clinical Molecular Pathology and Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara.
A
A
Sirmaci
H
H
Oztürkmen-Akay
S
S
Erbek
A
A
Incesulu
D
D
Duman
S
S
Taşir-Yilmaz
H
H
Ozdağ
M
M
Tekin
D019943:Amino Acid Substitution; D001483:Base Sequence; D000072259:Connexin 26; D017630:Connexins; D004247:DNA / Q000032:analysis / Q000235:genetics; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D005820:Genetic Testing; D015894:Genome, Human; D006239:Haplotypes; D006319:Hearing Loss, Sensorineural / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D014421:Turkey / Q000453:epidemiology
D017630:Connexins; C000607042:GJB2 protein, human; D008565:Membrane Proteins; C466299:TMIE protein, human; D000072259:Connexin 26; D004247:DNA