Analysis of the genotype-phenotype correlation of MYO15A variants in Chinese non-syndromic hearing loss patients.
Analysis of the genotype-phenotype correlation of MYO15A variants in Chinese non-syndromic hearing loss patients.
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中国非综合征性听力损失患者MYO15A变异基因型与表型相关性分析
DOI：
10.1186/s12920-022-01201-3
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发表时间：
2022-03-26
影响因子：
2.7
通讯作者：
Dai P
中科院分区：
文献类型：
--
作者：
Fu Y;Huang S;Gao X;Han M;Wang G;Kang D;Yuan Y;Dai P
MYO15A 基因突变是全球公认的常染色体隐性遗传非综合征性感音神经性听力损失 (NSHL) 的原因。在这里，我们研究了 MYO15A 变异在一组中国 NSHL 病例中的作用和基因型-表型相关性。该研究纳入了 2263 例中国 NSHL 病例中的 81 例，其中 81 例具有明显的 MYO15A 变异，这些病例接受了下一代测序 (NGS)。我们调查了 MYO15A 变异与听力损失的严重程度、进展和发病年龄的关系，并将其与之前不同国家的报告进行了比较。根据截断变异的数量将病例分为2组：2个截断变异、1个截断变异和1个非截断变异、2个非截断变异，并比较各组间HL的严重程度。 MYO15A 占所有 NSHL 病例的 3.58% (81/2263)。我们分析了 81 例 MYO15A 相关 NSHL 病例，其中 73 例患有先天性双侧、对称或重度至极重度听力损失 (HL)，然而，其中 2 例患有舌后、不对称、轻度或中度 HL。在所有 MYO15A 结构域中鉴定出 102 个变异，其中 76.47% (78/102) 是新的。最常见的检测到的变异类型是错义（44/102，43.14％），其次是移码（27/102，26.47％），无义（14/102，13.72％），剪接位点（10/102，9.80％），框内（4/102，3.92％），非编码（2/102， 1.96%）和同义（1/102，0.98%）。在 12 例病例中检测到最常见的变异 c.10245_10247delCTC。我们观察到，位于其 N 端、运动和 FERM 域的 MYO15A 变体会导致部分耳聋，并在低频下具有更好的残余听力。双等位基因截短变异34例，单等位基因截短变异37例，双等位非截短变异13例。双等位基因非截短变异组的病例数最少（12/81），其中大多数（10/12）患有严重的NSHL。 MYO15A是中国NSHL的主要基因。 MYO15A 变异病例大多表现为早发、对称、重度至极重度听力损失。这项研究是迄今为止规模最大的研究，重点评估 MYO15A 基因变异之间的基因型-表型相关性及其对 NSHL 结果的影响。双等位非截短MYO15A变异通常会导致严重的HL，而具有一两个截短MYO15A变异的病例往往会增加HL的风险。尽管如此，仍需要进一步调查来阐明听力损失不同严重程度和进展率的原因以及这些病例中检测到的 MYO15A 变异。在线版本包含可在 10.1186/s12920-022-01201-3 获取的补充材料。
Mutations in the MYO15A gene are a widely recognized cause of autosomal recessive non-syndromic sensorineural hearing loss (NSHL) globally. Here, we examined the role and the genotype–phenotype correlation of MYO15A variants in a cohort of Chinese NSHL cases. Eighty-one cases with evidenced MYO15A variants from the 2263 Chinese NSHL cases, who underwent next-generation sequencing (NGS), were enrolled in the study. We investigated the association of MYO15A variants with the severity, progression and age of onset of hearing loss, as well as compared it to the previous reports in different nationalities. The cases were divided into groups according to the number of truncating variants: 2 truncating, 1 truncating and 1 non-truncating, 2 non-truncating variants, and compared the severity of HL among the groups. MYO15A accounted for 3.58% (81/2263) of all NSHL cases. We analyzed 81 MYO15A-related NSHL cases, 73 of whom were with congenital bilateral, symmetric or severe-to-profound hearing loss (HL), however, 2 of them had a postlingual, asymmetric, mild or moderate HL. There were 102 variants identified in all MYO15A structural domains, 76.47% (78/102) of whom were novel. The most common types of detected variants were missense (44/102, 43.14%), followed by frameshift (27/102, 26.47%), nonsense (14/102, 13.72%), splice site (10/102, 9.80%), in frame (4/102, 3.92%), non-coding (2/102, 1.96%) and synonymous (1/102, 0.98%). The most recurrent variant c.10245_10247delCTC was detected in 12 cases. We observed that the MYO15A variants, located in its N-terminal, motor and FERM domains, led to partial deafness with better residual hearing at low frequencies. There were 34 cases with biallelic truncating variants, 37 cases with monoallelic truncating variants, and 13 cases with biallelic non-truncating variants. The biallelic non-truncating variants group had the least number of cases (12/81), and most of them (10/12) were with profound NSHL. MYO15A is a major gene responsible for NSHL in China. Cases with MYO15A variants mostly showed early-onset, symmetric, severe-to-profound hearing loss. This study is by far the largest focused on the evaluation of the genotype–phenotype correlations among the variants in the MYO15A gene and its implication in the outcome of NSHL. The biallelic non-truncating MYO15A variants commonly caused profound HL, and the cases with one or two truncating MYO15A variants tended to increase the risk of HL. Nevertheless, further investigations are needed to clarify the causes for the variable severities and progression rates of hearing loss and the detected MYO15A variants in these cases. The online version contains supplementary material available at 10.1186/s12920-022-01201-3.
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影响因子：
3.7
作者：
Chen Y;Wang Z;Wang Z;Chen D;Chai Y;Pang X;Sun L;Wang X;Yang T;Wu H
通讯作者：
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DOI：
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影响因子：
7.4
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