Genetic epidemiological studies of congenital/prelingual deafness in Turkey: Population structure and mating type are major determinants of mutation identification

Abstract

In order to evaluate the genetic epidemiology of deafness in Turkey, we first analyzed the pedigree data obtained from 2,169 families whose children were students of the schools for hearing loss/deafness in 31 cities of Turkey. Single major locus segregation analysis was performed after families were grouped according to hearing status of the parents. The results showed that sporadic phenocopies, autosomal dominant, and autosomal recessive transmission account for 18.2%, 4.9%, and 76.9% of the cases respectively, after exclusion of probands with unequivocal evidence for environmental etiologies. The high frequency of autosomal recessive transmission of this study differs from those of previous ones in Western populations. We subsequently analyzed the data from a subset of 574 unrelated families that were evaluated clinically, including mutation analysis of the GJB2 gene in 406 probands. Biallelic mutations were detected in 22.4% of all probands. They were present in 68.8% of probands whose parents were both deaf, yet in only 9.3% when both parents were hearing and consanguineous without a family history of deafness. Our study shows that GJB2 is the major gene for deafness in Turkey and was amplified in deaf by deaf matings, since assortative mating preferentially affects common genes. Deafness in the remaining families appears to result from mutations at many loci that are less frequent causes of deafness, because consanguinity has a proportionally greater effect on rare genes. Conclusions of this study may be relevant to other populations where consanguineous or assortative mating is present with various frequencies.

Identification of Copy Number Variants Through Whole-Exome Sequencing in Autosomal Recessive Nonsyndromic Hearing Loss

“…Overall, causative CNVs were present in 2.6% of the 78 studied families. Causative GJB2 mutations are present in 19% of multiplex and consanguineous Turkish families with ARNSHL (Tekin and Arici, 2007). Thus, the frequency of causative CNVs in this population is 2.1% (95% CI: 0% to 4.9%).…”

The Prevalence of Gap Junction Protein Beta 2 (GJB2) Mutations in Non Syndromic Sensorineural Hearing Loss in Çukurova Region

“…Because kin marriage is common in our country and because families live in isolation in certain regions, the frequency of rare genes responsible for autosomal recessive hearing loss is enhanced. Therefore, these rates, in our country, are 93.4% for autosomal recessive heritage and 6.6% for autosomal dominant heritage [3] .…”

“…Hearing loss is seen in every 1000 live births because of genetic conditions (50%-60%), infection, trauma, and premature birth [1,2] . However, these rates in our country differ, and they are 76.8% for genetic reasons and 23.2% for environmental reasons [3] .…”

Hearing Screening Program in the Newborn and Management: Review

“…23 Ülke-mizde saptanan işitme kayıplarının ise %51'i genetik, %34'ü idiyopatik ve %15'i edinilmiş olup, bu hastaların %94'ünde otozomal resesif, %6'sında otozomal dominant geçiş tanımlanmış ve en sık görülen mutasyon GJB2 (kromozom 13q12, 35delG, 167delT, 235delC) olarak rapor edilmiştir. [24][25][26] Yin ve ark.nın doğurganlık çağında, eşiyle akrabalığı olmayan ve işitme kaybı öyküsü bulunmayan 7.263 Çinli kadın üzerinde yaptığı bir çalışmada; işitme kaybı için patojen genetik mutasyon (GJB2 "235 del C %1,76", GJB3, SLC26A4 "919-2A>G %1,24" ve mtDNA 12S rRNA) taşıyıcılığı %4,17 olarak bildirilmiştir. 27 Aynı çalışmada, GJB2 ve SLC26A4 genlerinde farklı heterozigot mutasyon saptanan ailelerden alınan fetal ör-neklemlerde (koryonik villüs, amniyosentez veya fetal kanda); fetal heterozigot mutasyon saptananlarda işitmenin normal, ancak homozigot mutasyon saptananlarda ciddi işitme kaybı görülebileceği vurgulanmaktadır.…”