Frei Klemens, Ramsebner Reinhard, Lucas Trevor, Baumgartner Wolf-Dieter, Schoefer Christian, Wachtler Franz J, Kirschhofer Karin
Department of Otorhinolaryngology, Medical University of Vienna, AKH-8J, Waehringer Gürtel 18-20, Vienna A-1090, Austria.
Hear Res. 2004 Oct;196(1-2):115-8. doi: 10.1016/j.heares.2004.07.001.
Genetically caused congenital deafness is a common trait affecting 1 in 2000 newborn children and is predominantly inherited in an autosomal recessive fashion. Genes such as the gap junction protein beta 2 (GJB2) encoding for Connexin (Cx26) and GJB6 (Cx30) are known to cause sensorineural deafness. Autosomal recessive deafness has been linked both to the monogenetic occurrence of mutated GJB2 or the GJB6 deletion del(GJB6-D13S1830) and digenic GJB2/del(GJB6-D13S1830) inheritance. Monogenetic GJB2 alterations are responsible for 25.5% of deafness in the eastern Austrian population. An additional 9.8% are heterozygous carriers of a single GJB2 mutation which is not responsible for deafness alone. Del(GJB6-D13S1830) and GJB2/del(GJB6-D13S1830) mutations have been shown to be the second most frequent cause of deafness in different populations. To address the question of the relevance of mutations in GJB6 either as a monogenetic or a digenic GJB2/del(GJB6-D13S1830) cause of deafness in this population, 76 unrelated individuals (33 families and 43 sporadic cases) were screened using PCR strategies. Similar to studies in other hard of hearing populations with similar or lower carrier frequencies of single GJB2 mutations, the presence of del(GJB6-D13S1830) was not detected in any individual within the patient group. Data therefore exclude a digenetic association of del(GJB6-D13S1830) with heterozygous GJB2 mutations as a cause of deafness in a representative sample of the population from Eastern Austria.
遗传性先天性耳聋是一种常见特征,每2000名新生儿中就有1人受其影响,且主要以常染色体隐性方式遗传。已知编码连接蛋白(Cx26)的间隙连接蛋白β2(GJB2)和GJB6(Cx30)等基因会导致感音神经性耳聋。常染色体隐性耳聋与GJB2突变的单基因发生或GJB6缺失del(GJB6-D13S1830)以及双基因GJB2/del(GJB6-D13S1830)遗传均有关联。单基因GJB2改变导致奥地利东部人群中25.5%的耳聋病例。另外9.8%是单个GJB2突变的杂合携带者,该突变本身并不导致耳聋。Del(GJB6-D13S1830)和GJB2/del(GJB6-D13S1830)突变已被证明是不同人群中第二常见的耳聋原因。为了探讨GJB6突变作为单基因或双基因GJB2/del(GJB6-D13S1830)导致该人群耳聋的相关性问题,采用PCR策略对76名无亲缘关系的个体(33个家庭和43例散发病例)进行了筛查。与其他单GJB2突变携带者频率相似或更低的听力障碍人群的研究结果类似,在患者组的任何个体中均未检测到del(GJB6-D13S1830)的存在。因此,数据排除了在奥地利东部人群的代表性样本中,del(GJB6-D13S1830)与杂合GJB2突变的双基因关联作为耳聋原因的可能性。