Tekin Mustafa, Arici Zehra Serap
Division of Clinical Molecular Pathology and Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey.
Am J Med Genet A. 2007 Jul 15;143A(14):1583-91. doi: 10.1002/ajmg.a.31702.
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.
为了评估土耳其耳聋的遗传流行病学，我们首先分析了从土耳其31个城市中孩子就读于听力损失/失聪学校的2169个家庭获得的家系数据。在根据父母的听力状况对家庭进行分组后，进行了单主基因座分离分析。结果显示，在排除有明确环境病因证据的先证者后，散发性表型模拟、常染色体显性和常染色体隐性遗传分别占病例的18.2%、4.9%和76.9%。本研究中常染色体隐性遗传的高频率与西方人群先前的研究结果不同。我们随后分析了574个经过临床评估的无关家庭的子集数据，包括对406名先证者进行GJB2基因的突变分析。在所有先证者中，22.4%检测到双等位基因突变。在父母均为聋人的先证者中，该突变的出现率为68.8%，而在父母听力正常且有血缘关系但无耳聋家族史的先证者中，仅为9.3%。我们的研究表明，GJB2是土耳其耳聋的主要基因，并且在聋人与聋人的婚配中被扩增，因为选型交配优先影响常见基因。其余家庭的耳聋似乎是由许多导致耳聋频率较低的基因座突变引起的，因为近亲结婚对罕见基因的影响比例更大。本研究的结论可能与其他存在不同频率近亲或选型交配的人群相关。
