Huculak C, Bruyere H, Nelson T N, Kozak F K, Langlois S
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Am J Med Genet A. 2006 Nov 15;140(22):2394-400. doi: 10.1002/ajmg.a.31486.
Sensorineural hearing loss (SNHL) is the most common inherited sensory disorder, reported in 1-3 of every 1,000 births. It has been estimated that 50% of all cases of prelingual SNHL are genetically determined. There is tremendous genetic heterogeneity, with multiple dominant and recessive loci. Mutations of the gap junction beta-2 gene (GJB2) emerge as a leading cause of autosomal recessive non-syndromic SNHL. Over 90 sequence alterations have been reported, the pathogenicity of some of them being unknown or unclear. The status of the V37I allele of connexin 26 (GJB2 amino acid product) with regards to its association with SNHL has been controversial. This study examines the pathogenicity of V37I by comparing the frequency of this allele in 40 patients with SNHL of Chinese and Caucasian descent with the frequency of the allele in 100 anonymized, ethnically matched controls. The V37I allele was identified in 43.75 and 11.5% of the patient and control alleles of Chinese ethnicity, respectively, but was not found in either Caucasian cohort. We also compiled the audiograms of 15 individuals with SNHL homozygous for the V37I allele, and showed that these individuals present with a mild to moderate SNHL. These results indicate that (1) the V37I allele is common in individuals of Chinese descent but rarely present in individuals of Caucasian decent; and (2) the V37I allele is pathogenic, but produces milder hearing loss compared to nonsense mutations of connexin 26 such as the 35delG mutation.
感音神经性听力损失（SNHL）是最常见的遗传性感觉障碍，每1000例出生中就有1 - 3例报告。据估计，所有语前SNHL病例中有50%是由基因决定的。存在巨大的遗传异质性，有多个显性和隐性基因座。缝隙连接β-2基因（GJB2）突变成为常染色体隐性非综合征性SNHL的主要原因。已报道了90多种序列改变，其中一些的致病性尚不清楚。连接蛋白26（GJB2氨基酸产物）的V37I等位基因与SNHL的关联一直存在争议。本研究通过比较40例中国和白种人后裔SNHL患者中该等位基因的频率与100例匿名的、种族匹配的对照者中该等位基因的频率，来检测V37I的致病性。V37I等位基因分别在43.75%的中国患者等位基因和11.5%的中国对照者等位基因中被鉴定出，但在两个白种人群体中均未发现。我们还汇总了15例V37I等位基因纯合的SNHL个体的听力图，并表明这些个体表现为轻度至中度SNHL。这些结果表明：（1）V37I等位基因在华裔个体中常见，但在白种人个体中很少出现；（2）V37I等位基因具有致病性，但与连接蛋白26的无义突变（如35delG突变）相比，产生的听力损失较轻。
