Bouwer Sonja, Angelicheva Dora, Chandler David, Seeman Pavel, Tournev Ivailo, Kalaydjieva Luba
Western Australian Institute for Medical Research and Centre for Medical Research, The University of Western Australia, Perth, Australia.
Genet Test. 2007 Winter;11(4):455-8. doi: 10.1089/gte.2007.0048.
Mutations in the GJB2 gene are the most common cause of autosomal recessive nonsyndromic hearing loss and occur in approximately 20% of all cases of prelingual deafness. Previous studies of Roma/Gypsies in Slovakia, the Czech Republic, and Spain have shown that W24X, the most common GJB2 mutation in India, is also the prevalent molecular defect in the Gypsy population. The reported W24X frequencies vary broadly from 23% to 93% of Gypsy mutant alleles, likely reflecting local founder effects, drift, and differential admixture in the subisolates of this genetically structured population. Our goal was to provide more representative data on W24X carrier rates in European Gypsies, which can inform individual diagnostic investigations and public health initiatives across countries. Mutation testing in 603 control subjects of Gypsy ethnicity, representing 8 traditional subisolates in southeastern Europe and 4 additional European regions revealed that W24X is spread across subisolates, as expected for an ancestral founder mutation. While variation between subisolates does exist, the average carrier rates, overall and in the major linguistic/migrational categories of Balkan Gypsies, Vlax Roma, and west European Gypsies, are consistently in the 4%-5% range. The results place W24X among the three most common founder mutations in the Gypsies, and classify them as one of the high-risk populations for prelingual deafness. Higher demands on language acquisition in this bilingual population, together with poorer quality of health care compared to autochthonous Europeans, make the consequences of congenital deafness even more damaging than is usually the case. Neonatal screening for W24X among Gypsies would be a justified and cost-effective public health intervention.
GJB2基因突变是常染色体隐性非综合征性听力损失的最常见原因，约占所有语前聋病例的20%。此前在斯洛伐克、捷克共和国和西班牙对罗姆人/吉普赛人的研究表明，W24X作为印度最常见的GJB2突变，也是吉普赛人群中普遍存在的分子缺陷。报道的W24X频率在吉普赛突变等位基因的23%至93%之间广泛变化，这可能反映了这个基因结构人群的亚隔离群体中的局部奠基者效应、基因漂变和不同的混合情况。我们的目标是提供关于欧洲吉普赛人W24X携带者率的更具代表性的数据，这可以为各国的个体诊断调查和公共卫生倡议提供信息。对603名吉普赛族对照受试者进行的突变检测，这些受试者代表了东南欧的8个传统亚隔离群体以及另外4个欧洲地区，结果显示W24X如预期的那样在各亚隔离群体中广泛分布，是一个祖传的奠基者突变。虽然亚隔离群体之间确实存在差异，但总体以及巴尔干吉普赛人、弗拉克斯罗姆人和西欧吉普赛人等主要语言/迁徙类别的平均携带者率始终在4% - 5%的范围内。研究结果表明W24X是吉普赛人中最常见的三种奠基者突变之一，并将他们归类为语前聋的高危人群之一。与本地欧洲人相比，这个双语人群对语言习得的要求更高，同时医疗保健质量较差，这使得先天性耳聋的后果比通常情况更具破坏性。对吉普赛人进行W24X新生儿筛查将是一项合理且具有成本效益的公共卫生干预措施。
