Whole exome analysis of patients in Japan with hearing loss reveals high heterogeneity among responsible and novel candidate genes.
Whole exome analysis of patients in Japan with hearing loss reveals high heterogeneity among responsible and novel candidate genes.
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日本听力损失患者的全外显子组分析揭示了负责和新候选基因之间的高度异质性。
DOI：
10.1186/s13023-022-02262-4
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发表时间：
2022-03-05
影响因子：
3.7
通讯作者：
Matsunaga T
中科院分区：
文献类型：
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作者：
Mutai H;Momozawa Y;Kamatani Y;Nakano A;Sakamoto H;Takiguchi T;Nara K;Kubo M;Matsunaga T
遗传性耳聋是由异质性遗传基因引起的，目前已鉴定出100多个耳聋基因，而且这个数字还在增加。为了检测多个耳聋基因中的致病变异，除了与听力损失相关的新的候选基因外，还应用了全外显子组测序(WES)，然后对分为四个层次的基因进行了优先排序。来自非综合征性或综合征性耳聋家系的三人(n = ，72人)接受WES检查。根据美国医学遗传学和基因组学指南进行分离分析和解释，在21个家系中发现了11个耳聋基因(STRC、MYO15A、CDH23、PDZD7、PTPN11、SOX10、EYA1、MYO6、OTOF、OTOG和ZNF335)的候选致病变异。家系遗传和遗传遗传在1个家系中存在差异。此外，在10个家系中筛选出8个基因(Slc12a2、BAIAP2L2、HKDC1、SVEP1、CACNG1、GTPBP4、PCNX2和TBC1D8)作为单候选基因。我们的发现表明，WES数据的四级评估是有效的，除了已知耳聋基因的致病变异外，还可以检测与听力损失相关的新候选基因。网上版载有补充材料，可在10.1186/s13023-022-02262-4查阅。
Heterogeneous genetic loci contribute to hereditary hearing loss; more than 100 deafness genes have been identified, and the number is increasing. To detect pathogenic variants in multiple deafness genes, in addition to novel candidate genes associated with hearing loss, whole exome sequencing (WES), followed by analysis prioritizing genes categorized in four tiers, were applied. Trios from families with non-syndromic or syndromic hearing loss (n = 72) were subjected to WES. After segregation analysis and interpretation according to American College of Medical Genetics and Genomics guidelines, candidate pathogenic variants in 11 previously reported deafness genes (STRC, MYO15A, CDH23, PDZD7, PTPN11, SOX10, EYA1, MYO6, OTOF, OTOG, and ZNF335) were identified in 21 families. Discrepancy between pedigree inheritance and genetic inheritance was present in one family. In addition, eight genes (SLC12A2, BAIAP2L2, HKDC1, SVEP1, CACNG1, GTPBP4, PCNX2, and TBC1D8) were screened as single candidate genes in 10 families. Our findings demonstrate that four-tier assessment of WES data is efficient and can detect novel candidate genes associated with hearing loss, in addition to pathogenic variants of known deafness genes. The online version contains supplementary material available at 10.1186/s13023-022-02262-4.
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影响因子：
16.6
作者：
Guo C;Ludvik AE;Arlotto ME;Hayes MG;Armstrong LL;Scholtens DM;Brown CD;Newgard CB;Becker TC;Layden BT;Lowe WL;Reddy TE
通讯作者：
Reddy TE
影响因子：
14.9
作者：
Desmet FO;Hamroun D;Lalande M;Collod-Béroud G;Claustres M;Béroud C
通讯作者：
Béroud C
影响因子：
4.8
作者：
Jensen, BC;Wang, Q;Parsons, M
通讯作者：
Parsons, M
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
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