Expansion of phenotypic spectrum of MYO15A pathogenic variants to include postlingual onset of progressive partial deafness.
Expansion of phenotypic spectrum of MYO15A pathogenic variants to include postlingual onset of progressive partial deafness.
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DOI：
10.1186/s12881-018-0541-9
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发表时间：
2018-02-27
影响因子：
--
通讯作者：
Choi BY
中科院分区：
文献类型：
--
作者：
Chang MY;Lee C;Han JH;Kim MY;Park HR;Kim N;Park WY;Oh DY;Choi BY
MYO 15 A变体，除了N-末端结构域中的那些，已被证明与先天性或语前重度至极重度听力损失（DFNB 3）相关，其最终需要在儿童早期植入人工耳蜗。最近，此类变体也被证明可能导致中度至重度听力损失。在此，我们还证明了一些MYO 15 A突变等位基因可以导致进行性部分性耳聋的舌后发作。两个多重韩国家庭（SB 246和SB 224），表现为语言后，进行性，部分耳聋的常染色体隐性遗传方式，被招募。SB 246家族的分子遗传学检测以平行方式在两个不同的管道中进行：先证者的129个已知耳聋基因的靶向外显子组测序（TES）和所有受影响受试者的全外显子组测序（WES）。仅对SB 224系列执行了前一个管道。执行包括结构变异的严格生物信息学分析，以研究任何致病变体。在SB 246家族中，两种不同的分子诊断管道提供了完全相同的候选变体：MYO 15 A的马达结构域中的c.5504G > A（p.R1835H）和FERM结构域中的c.10245_10247delCTC（p.S3417del）。在SB 224家族中，FERM结构域中的c.9790C > T（p.Q3264X）和c.10263C > G（p.I3421M）被检测为候选变体。某些MYO 15 A隐性变异可导致进行性部分性耳聋的语后发作。DFNB 3的表型谱应扩展到包括这种部分耳聋。较温和表型的机制可能是由于MYO 15 A的亚纯型等位基因或修饰基因的存在导致较温和的致病潜力。这值得进一步调查。本文的在线版本（10.1186/s12881-018-0541-9）包含补充材料，可供授权用户使用。
MYO15A variants, except those in the N-terminal domain, have been shown to be associated with congenital or pre-lingual severe-to-profound hearing loss (DFNB3), which ultimately requires cochlear implantation in early childhood. Recently, such variants have also been shown to possibly cause moderate-to-severe hearing loss. Herein, we also demonstrate that some MYO15A mutant alleles can cause postlingual onset of progressive partial deafness. Two multiplex Korean families (SB246 and SB224), manifesting postlingual, progressive, partial deafness in an autosomal recessive fashion, were recruited. Molecular genetics testing was performed in two different pipelines, in a parallel fashion, for the SB246 family: targeted exome sequencing (TES) of 129 known deafness genes from the proband and whole exome sequencing (WES) of all affected subjects. Only the former pipeline was performed for the SB224 family. Rigorous bioinformatics analyses encompassing structural variations were executed to investigate any causative variants. In the SB246 family, two different molecular diagnostic pipelines provided exactly the same candidate variants: c.5504G > A (p.R1835H) in the motor domain and c.10245_10247delCTC (p.S3417del) in the FERM domain of MYO15A. In the SB224 family, c.9790C > T (p.Q3264X) and c.10263C > G (p.I3421M) in the FERM domain were detected as candidate variants. Some recessive MYO15A variants can cause postlingual onset of progressive partial deafness. The phenotypic spectrum of DFNB3 should be extended to include such partial deafness. The mechanism for a milder phenotype could be due to the milder pathogenic potential from hypomorphic alleles of MYO15A or the presence of modifier genes. This merits further investigation. The online version of this article (10.1186/s12881-018-0541-9) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Moy AJ;Wiersma MP;Choi B
通讯作者：
Choi B
全外显子组测序鉴定出常染色体隐性听力损失患者 MYO15A 基因的新型复合杂合突变
影响因子：
7.4
作者：
Gao X;Zhu QY;Song YS;Wang GJ;Yuan YY;Xin F;Huang SS;Kang DY;Han MY;Guan LP;Zhang JG;Dai P
通讯作者：
Dai P
DOI：
10.1073/pnas.2334417100
发表时间：
2003-11-25
影响因子：
11.1
作者：
Belyantseva, IA;Boger, ET;Friedman, TB
通讯作者：
Friedman, TB
影响因子：
1.4
作者：
Cengiz, F. Basak;Duman, Duygu;Tekin, Mustafa
通讯作者：
Tekin, Mustafa
土耳其听力损失家庭中的 MY015A（DFNB3）突变和新型运动结构域突变的功能建模
影响因子：
2
作者：
Kalay, Ersan;Uzumcu, Abdullah;Kremer, Hannie
通讯作者：
Kremer, Hannie