Investigation of the hearing levels of siblings affected by a single GJB2 variant: Possibility of genetic modifiers
Investigation of the hearing levels of siblings affected by a single GJB2 variant: Possibility of genetic modifiers
复制标题
DOI：
10.1016/j.ijporl.2021.110840
复制
发表时间：
2021-07-19
影响因子：
1.5
通讯作者：
Matsunaga, Tatsuo
中科院分区：
文献类型：
--
作者：
Hosoya, Makoto;Fujioka, Masato;Matsunaga, Tatsuo
目的：GJB2基因变异可导致常染色体隐性遗传性耳聋(DFNB1)。有证据表明GJB2变异的基因-表型相关；然而，几种基因可能导致不同程度的听力损失，可能归因于遗传或环境背景的差异。由于兄弟姐妹有大约50%的遗传背景相同，并且通常有共同的环境背景，对具有特定GJB2变异的兄弟姐妹的表型分析可能揭示与表型变异相关的因素。此前还没有关于携带单一GJB2基因的兄弟姐妹之间听力差异的分析。在这里，我们研究了具有单一GJB2变异的兄弟姐妹之间的听力差异，这可能导致不同程度的听力损失。方法：我们检测了16对GJB2基因c.235delC变异纯合子同胞的听力水平。通过听觉评估发现兄弟姐妹之间听力的差异。结果：5对兄弟姐妹的声学阈值平均相差30分贝，而其余11对兄弟姐妹的平均阈值相差约10分贝。听力损失从中度到重度不等。结论：我们的结果表明，GJB2c.235delC纯合子与听觉敏锐度相关的程度可能有所不同；然而，在大约70%的年幼兄弟姐妹中，其听力与第一个孩子大致相同，尽管不同家庭的听力损失谱不同。这些结果表明，遗传背景的差异可能改变与纯合子GJB2 c.235delC相关的表型。
Objective: Variants in GJB2 can cause autosomal recessive deafness (DFNB1). There is evidence for genotype-phenotype correlations of GJB2 variants; however, several genotypes can cause varying levels of hearing loss likely attributable to differences in genetic or environmental background. As siblings share approximately 50% of their genetic background and usually have a common environmental background, analysis of phenotypes of siblings with a specific GJB2 variant may reveal factors relevant to phenotypic variation. There have been no previous analyses of differences in hearing among siblings carrying a single GJB2 genotype. Here, we investigated hearing differences between siblings with a single GJB2 variant, which can cause various levels of hearing loss. Methods: We examined hearing levels in 16 pairs of siblings homozygous for the c.235delC variant of GJB2. Differences in hearing acuity between sibling pairs were detected by auditory evaluation. Results: Average differences in acoustic threshold >30 dB were observed between five pairs of siblings, whereas the remaining 11 pairs had average threshold values within approximately 10 dB of one another. Hearing loss varied from moderate to profound. Conclusion: Our results indicate that auditory acuity associated with homozygosity for GJB2 c.235delC can vary in degree; however, in approximately 70% of younger siblings, it was approximately the same as that in the first child, despite a diverse spectrum of hearing loss among different families. These results suggest that differences in genetic background may modify the phenotype associated with homozygous GJB2 c.235delC.