Connexin-26-associated deafness: Phenotypic variability and progression of hearing loss
Connexin-26-associated deafness: Phenotypic variability and progression of hearing loss
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DOI：
10.1097/gim.0b013e3181d0d42b
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发表时间：
2010-03-01
影响因子：
8.8
通讯作者：
Chang, Kay W.
中科院分区：
文献类型：
--
作者：
Chan, Dylan K.;Schrijver, Iris;Chang, Kay W.
目的：评估一组连接蛋白26（GJB 2）相关常染色体隐性听力损失儿童随时间推移的基因型-表型相关性。研究方法：从GJB 2纯合或复合杂合突变个体数据库中确定了52名儿童，并对其耳鼻喉科和系列听力评估进行了图表审查。通过适当的统计分析，在该组成员中确定了基因型-表型相关性。结果：听力损失在GJB 2中有两个截短突变的个体中最严重，在有两个非截短突变的个体中最轻。在所有受试者中，24%的受试者通过连续测听直接观察到进行性听力损失，当包括正常新生儿听力筛查和随后听力损失的受试者时，总共有28%的受试者建议进行性听力损失。进展在p.V37I等位基因纯合性或复合杂合性与截短等位基因携带者中特别常见;这些儿童主要是亚洲血统，表现出轻度、缓慢进行性听力损失。结论：GJB 2相关性听力损失的表型与基因型相关，截短突变导致更严重的听力损失。听力损失的进展并不罕见，特别是与p.V37I等位基因相关。这些结果表明，密切的听力随访与GJB 2相关的隐性听力损失的患者是必要的。Genet Med 2010：12（3）：174-181.
Purpose: To evaluate genotype-phenotype correlation over time for a cohort of children with connexin-26 (GJB2)-associated autosomal recessive hearing loss. Methods: Fifty-two children were identified from a database of individuals with homozygous or compound heterozygous mutations in GJB2 and subjected to chart review of their otolaryngologic and serial audiometric evaluations. Genotype-phenotype correlations were identified among the members of this group by appropriate statistical analyses. Results: Hearing loss was most severe in individuals with two truncating mutations in GJB2 and mildest in those with two nontruncating mutations. Progressive hearing loss was seen directly by serial audiometry in 24% of all subjects, and suggested in a total of 28% when those with normal newborn hearing screens and subsequent hearing loss were included. Progression was particularly common among carriers of the p. V37I allele either in homozygosity or in compound heterozygosity with a truncating allele; these children are primarily of Asian descent and demonstrate mild, slowly progressive hearing loss. Conclusions: Phenotype in GJB2-associated hearing loss is correlated with genotype, with truncating mutations giving rise to more severe hearing loss. Progression of hearing loss is not uncommon, especially in association with the p. V37I allele. These results suggest that close audiometric follow-up is warranted for patients with GJB2-associated recessive hearing loss. Genet Med 2010:12(3):174-181.