Novel mutations in the connexin 26 gene (GJB2) responsible for childhood deafness in the Japanese population.
Novel mutations in the connexin 26 gene (GJB2) responsible for childhood deafness in the Japanese population.
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DOI：
10.1002/(sici)1096-8628(20000117)90:2
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发表时间：
2000-01
期刊：
影响因子：
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通讯作者：
Takayuki Kudo;K. Ikeda;S. Kure;Y. Matsubara;T. Oshima;Kenichi Watanabe;T. Kawase;K. Narisawa;T. Takasaka
中科院分区：
文献类型：
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作者：
Takayuki Kudo;K. Ikeda;S. Kure;Y. Matsubara;T. Oshima;Kenichi Watanabe;T. Kawase;K. Narisawa;T. Takasaka
连接蛋白26基因（GJB2）编码一种间隙连接蛋白并在内耳中表达，该基因的突变已被证明是高加索人非综合征遗传性语前（幼儿）耳聋的主要原因。我们对39名日本语前耳聋患者（第一组）、39名日本语后进行性感音神经性听力损失患者（第二组）和63名听力正常的日本人（第三组）的GJB2基因进行了测序。在第1组中发现了三个新的突变：单核苷酸缺失（235delC）， 16-bp缺失（176-191 del(16)）和无义突变（Y136X）。235delC突变最为常见，在10个突变等位基因中占7个。对203名无亲缘关系的正常个体进行这三种突变的筛查表明，日本人群中235delC突变的携带频率为2/203。2组患者未发现基因突变。我们还发现了两个新的多态性（E114G和I203T）以及两个先前报道的多态性（V27I和v37i）。用这四种多态性进行基因分型，可以将正常的日本等位基因分为七个单倍型。在4例患者中发现的所有235delC突变等位基因仅位于1型单倍型上。这些发现表明GJB2突变也是导致日本语前耳聋的原因。
Mutations in the connexin 26 gene (GJB2), which encodes a gap-junction protein and is expressed in the inner ear, have been shown to be responsible for a major part of nonsyndromic hereditary prelingual (early-childhood) deafness in Caucasians. We have sequenced the GJB2 gene in 39 Japanese patients with prelingual deafness (group 1), 39 Japanese patients with postlingual progressive sensorineural hearing loss (group 2), and 63 Japanese individuals with normal hearing (group 3). Three novel mutations were identified in group 1: a single nucleotide deletion (235delC), a 16-bp deletion (176-191 del (16)), and a nonsense mutation (Y136X) in five unrelated patients. The 235delC mutation was most frequently observed, accounting for seven alleles in 10 mutant alleles. Screening of 203 unrelated normal individuals for the three mutations indicated that the carrier frequency of the 235delC mutation was 2/203 in the Japanese population. No mutation was found in group-2 patients. We also identified two novel polymorphisms (E114G and I203T) as well as two previously reported polymorphisms (V27I andV37I). Genotyping with these four polymorphisms allowed normal Japanese alleles to be classified into seven haplotypes. All 235delC mutant alleles identified in four patients resided only on haplotype type 1. These findings indicate that GJB2 mutations are also responsible for prelingual deafness in Japan.