Department of Otolaryngology-Head and Neck Surgery, Lucille Packard Children's Hospital, Stanford University Hospital and Clinics, Stanford, California 94305, USA.
Genet Med. 2010 Mar;12(3):174-81. doi: 10.1097/GIM.0b013e3181d0d42b.
To evaluate genotype-phenotype correlation over time for a cohort of children with connexin-26 (GJB2)-associated autosomal recessive hearing loss.
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.
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.
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.
评估一组连接蛋白 26（GJB2）相关常染色体隐性遗传性耳聋患者的基因型-表型相关性随时间的变化。
从 GJB2 纯合或复合杂合突变个体的数据库中确定了 52 名儿童，并对其耳鼻喉科和系列听力评估图表进行了回顾。通过适当的统计分析，确定了该组中成员之间的基因型-表型相关性。
GJB2 中存在两个截断突变的个体的听力损失最严重，存在两个非截断突变的个体的听力损失最轻。24%的所有受试者通过连续听力测试直接观察到进行性听力损失，当包括新生儿听力筛查正常但随后听力下降的受试者时，总共有 28%的受试者被认为存在进行性听力损失。在 p.V37I 等位基因的携带者中，特别是在纯合或与截断等位基因复合杂合的情况下，进展更为常见；这些儿童主要来自亚洲，表现为轻度、缓慢进展的听力损失。
GJB2 相关听力损失的表型与基因型相关，截断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，GJB2 相关隐性遗传性耳聋患者需要密切进行听力随访。
