Pandya Arti, Arnos Kathleen S, Xia Xia J, Welch Katherine O, Blanton Susan H, Friedman Thomas B, Garcia Sanchez Guillermina, Liu MD Xiu Z, Morell Robert, Nance Walter E
Department of Human Genetics, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Genet Med. 2003 Jul-Aug;5(4):295-303. doi: 10.1097/01.GIM.0000078026.01140.68.
Profound hearing loss occurs with a frequency of 1 in 1000 live births, half of which is genetic in etiology. The past decade has witnessed rapid advances in determining the pathogenesis of both syndromic and nonsyndromic deafness. The most significant clinical finding to date has been the discovery that mutations of GJB2 at the DFNB1 locus are the major cause of profound prelingual deafness in many countries. 1 More recently, GJB2 mutations have been shown to cause deafness when present with a deletion of the GJB6 gene. We report on the prevalence of GJB2 and GJB6 mutations in a large North American Repository of DNA from deaf probands and document the profound effects of familial ethnicity and parental mating types on the frequency of these mutations in the population.
Deaf probands were ascertained through the Annual Survey of Deaf and Hard of Hearing Children and Youth, conducted at the Research Institute of Gallaudet University. Educational, etiologic, and audiologic information was collected after obtaining informed consent. DNA studies were performed for the GJB2 and GJB6 loci by sequencing and PCR methods.
GJB2 mutations accounted for 22.2% of deafness in the overall sample but differed significantly among Asians, African-Americans and Hispanics and for probands from deaf by deaf and deaf by hearing matings, as well as probands from simplex and multiplex sibships of hearing parents. In our sample, the overall incidence of GJB2/GJB6 deafness was 2.57%.
GJB2 mutations account for a large proportion of deafness in the US, with certain mutations having a high ethnic predilection. Heterozygotes at the GJB2 locus should be screened for the GJB6 deletion as a cause of deafness. Molecular testing for GJB2 and GJB6 should be offered to all patients with nonsyndromic hearing loss.
重度听力损失在活产婴儿中的发生率为千分之一，其中一半病因是遗传性的。在过去十年中，在确定综合征性和非综合征性耳聋的发病机制方面取得了快速进展。迄今为止，最重要的临床发现是，DFNB1位点的GJB2基因突变是许多国家重度语前聋的主要原因。1最近，已证明GJB2基因突变与GJB6基因缺失同时存在时会导致耳聋。我们报告了北美一个大型聋人先证者DNA库中GJB2和GJB6基因突变的发生率，并记录了家族种族和父母交配类型对人群中这些突变频率的深远影响。
通过加劳德特大学研究所进行的年度聋儿及重听儿童和青少年调查确定聋人先证者。在获得知情同意后收集教育、病因和听力信息。通过测序和PCR方法对GJB2和GJB6位点进行DNA研究。
GJB2基因突变在总体样本中占耳聋的22.2%，但在亚洲人、非裔美国人和西班牙裔之间以及聋人之间、聋人与听力正常人交配的先证者以及听力正常父母的单纯型和复合型同胞关系的先证者之间存在显著差异。在我们的样本中，GJB2/GJB6耳聋的总体发生率为2.57%。
在美国，GJB2基因突变在耳聋中占很大比例，某些突变具有较高的种族倾向性。应筛查GJB2位点的杂合子是否存在GJB6基因缺失作为耳聋原因。应对所有非综合征性听力损失患者进行GJB2和GJB6的分子检测。
