Next-generation sequencing through multigene panel testing for the diagnosis of hereditary epidermolysis bullosa in Chinese population
Next-generation sequencing through multigene panel testing for the diagnosis of hereditary epidermolysis bullosa in Chinese population
复制标题
通过多基因组检测的下一代测序诊断中国人群遗传性大疱性表皮松解症
DOI：
10.1111/cge.13791
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发表时间：
2020-06-21
影响因子：
3.5
通讯作者：
Li, Ming
中科院分区：
文献类型：
--
作者：
Chen, Fuying;Huang, Linting;Li, Ming
大疱性表皮松解症（EB）是一种遗传性起泡疾病。我们进行了基于新一代测序的多基因面板检测，成功预测了100%的EB类型，包括36种EB单纯型（EBS）， 13种连接型EB (JEB)， 86种营养不良型EB （DEB）和3种Kindler EB。中国JEB和隐性DEB （RDEB）患者表型相对较轻；重症分别占45.5%和23.8%。我们在11个基因中发现了96个新的和49个复发的致病变异，尽管我们未能在1例JEB和5例RDEB患者中检测到第二种突变。我们在13名患有krt5突变的EBS患者的临床正常母亲中发现了一种新的p.E475K镶嵌突变，在19名显性DEB患者的临床正常亲属中发现了一种复发性p.G2034R镶嵌突变，在2名显性DEB患者的临床正常亲属中发现了一种新的p.G2043R镶嵌突变。这项研究表明，下一代技术可能是诊断EB的有效工具。
Epidermolysis bullosa (EB) is a heritable blistering disorder. We performed a next-generation sequencing-based multigene panel test and successfully predicted 100% of the EB types, including, 36 EB simplex (EBS), 13 junctional EB (JEB), 86 dystrophic EB (DEB), and 3 Kindler EB. Chinese JEB and recessive DEB (RDEB) patients have relatively mild phenotypes; for severe type separately accounts for 45.5% and 23.8%, respectively. We identified 96 novel and 49 recurrent pathogenic variants in 11 genes, although we failed to detect the second mutation in one JEB and five RDEB patients. We identified one novel p.E475K mosaic mutation in the clinically normal mother of one out of 13 EBS patients withKRT5mutations, one recurrent p.G2034R mosaic mutation, and one novel p.G2043R mosaic mutation in the clinically normal relatives of two out of 19 dominant DEB patients. This study shows that next-generation technology could be an effective tool in diagnosing EB.