Rabionet R, Zelante L, López-Bigas N, D'Agruma L, Melchionda S, Restagno G, Arbonés M L, Gasparini P, Estivill X
Deafness Research Group, Medical and Molecular Genetics Center, CGMM-IRO, Barcelona, Spain.
Hum Genet. 2000 Jan;106(1):40-4. doi: 10.1007/s004390051007.
Mutations in the GJB2 gene have been identified in many patients with childhood deafness, 35delG being the most common mutation in Caucasoid populations. We have analyzed a total of 576 families/unrelated patients with recessive or sporadic deafness from Italy and Spain, 193 of them being referred as autosomal recessive, and the other 383 as apparently sporadic cases (singletons). Of the 1,152 unrelated GJB2 chromosomes analyzed from these patients, 37% had GJB2 mutations. Twenty-three different mutations were detected (1 in-frame deletion, 4 nonsense, 5 frameshift, and 13 missense mutations). Mutation 35delG was the most common, accounting for 82% of all GJB2 deafness alleles. The relative frequency of 35delG in Italy and Spain was different, representing 88% of the alleles in Italian patients and only 55% in the Spanish cases. Eight non-35delG mutations were detected more than once (V37I, E47X, 167delT, L90P, 312de114, 334delAA, R143W, and R184P), with relative frequencies ranging between 0.5 and 1.6% of the GJB2 deafness alleles. The information based on conservation of amino acid residues, coexistence with a second GJB2 mutation or absence of the mutation in non-deaf control subjects, suggests that most of these missense changes should be responsible for the deafness phenotype.
在许多儿童期耳聋患者中已鉴定出GJB2基因突变，35delG是白种人群中最常见的突变。我们分析了来自意大利和西班牙的总共576个隐性或散发性耳聋家庭/非亲属患者，其中193例被诊断为常染色体隐性遗传，另外383例为明显的散发病例（单例）。在从这些患者中分析的1152条非亲属GJB2染色体中，37%存在GJB2突变。检测到23种不同的突变（1种框内缺失、4种无义突变、5种移码突变和13种错义突变）。35delG突变最为常见，占所有GJB2耳聋等位基因的82%。35delG在意大利和西班牙的相对频率不同，在意大利患者的等位基因中占88%，而在西班牙患者中仅占55%。有8种非35delG突变被多次检测到（V37I、E47X、167delT、L90P、312de114、334delAA、R143W和R184P），其相对频率在GJB2耳聋等位基因的0.5%至1.6%之间。基于氨基酸残基保守性、与第二个GJB2突变共存或在非耳聋对照受试者中不存在该突变的信息表明，这些错义变化中的大多数应与耳聋表型有关。
