Estivill X, Fortina P, Surrey S, Rabionet R, Melchionda S, D'Agruma L, Mansfield E, Rappaport E, Govea N, Milà M, Zelante L, Gasparini P
Department de Genètica, Centre de Genètica Medica i Molecular, Hospital Duran i Reynals, L'Hospitalet, Barcelona, Catalonia, Spain.
Lancet. 1998 Feb 7;351(9100):394-8. doi: 10.1016/S0140-6736(97)11124-2.
Hearing impairment affects one infant in 1000 and 4% of people aged younger than 45 years. Congenital deafness is inherited or apparently sporadic. We have shown previously that DFNB1 on chromosome 13 is a major locus for recessive deafness in about 80% of Mediterranean families and that the connexin-26 gene gap junction protein beta2 (GJB2) is mutated in DFNB1 families. We investigated mutations in the GJB2 gene in familial and sporadic cases of deafness.
We obtained DNA samples from 82 families from Italy and Spain with recessive non-syndromic deafness and from 54 unrelated participants with apparently sporadic congenital deafness. We analysed the coding region of the GJB2 gene for mutations. We also tested 280 unrelated people from the general populations of Italy and Spain for the frameshift mutation 35delG.
49% of participants with recessive deafness and 37% of sporadic cases had mutations in the GJB2 gene. The 35delG mutation accounted for 85% of GJB2 mutations, six other mutations accounted for 6% of alleles, and no changes in the coding region of GJB2 were detected in 9% of DFNB1 alleles. The carrier frequency of mutation 35delG among people from the general population was one in 31 (95% CI one in 19 to one in 87).
Mutations in the GJB2 gene are a major cause of inherited and apparently sporadic congenital deafness. Mutation 35delG is the most common mutation for sensorineural deafness. Identification of 35delG and other mutations in the GJB2 gene should facilitate diagnosis and counselling for the most common genetic form of deafness.
听力障碍影响着千分之一的婴儿以及45岁以下4%的人群。先天性耳聋可遗传或表现为散发。我们之前已经表明，13号染色体上的DFNB1是约80%地中海家庭中隐性耳聋的主要位点，并且连接蛋白26基因缝隙连接蛋白β2（GJB2）在DFNB1家庭中发生突变。我们调查了耳聋家族性和散发性病例中GJB2基因的突变情况。
我们从意大利和西班牙的82个患有隐性非综合征性耳聋的家庭以及54名明显散发先天性耳聋的无血缘关系参与者中获取了DNA样本。我们分析了GJB2基因的编码区以寻找突变。我们还对来自意大利和西班牙普通人群的280名无血缘关系的人进行了移码突变35delG检测。
49%的隐性耳聋参与者和37%的散发病例在GJB2基因中存在突变。35delG突变占GJB2突变的85%，其他六个突变占等位基因的6%，9%的DFNB1等位基因在GJB2编码区未检测到变化。普通人群中35delG突变的携带频率为31人中1人（95%可信区间为19人中1人至87人中1人）。
GJB2基因中的突变是遗传性和明显散发性先天性耳聋的主要原因。35delG突变是感音神经性耳聋最常见的突变。识别GJB2基因中的35delG和其他突变应有助于对最常见的遗传性耳聋形式进行诊断和咨询。
