摘要/Abstract

摘要： 目的 ·了解中国汉族人群 KRT9基因外显子编码区的主要变异类型及其致病性，为表皮松解性掌跖角化病临床基因诊断提供参考。方法 ·采用二代测序基因 Panel结合 Sanger测序验证策略对 278个中国汉族非表皮松解性掌跖角化病核心家系 834份样本的 KRT9基因全部外显子编码区进行检测；采用 SIFT、Polyphen-2及保守性分析对变异位点的致病性进行分析。结果 ·共检测到 12种 KRT9基因变异，同义和错义突变各 6种。各错义突变经 SIFT和 Polyphen-2预测、保守性分析及数据库查询等生物信息学分析均可归类为良性或可能良性变异。结论 ·在中国汉族人群 KRT9基因外显子编码区共检测到 6种错义突变，根据美国医学遗传学与基因组学学会变异分类标准，均为良性或可能良性变异；其中 c.1216T>C（p.C406R）位点的致病性与已有报道不一致，有待于进一步探讨。
关键词: KRT9基因, 表皮松解性掌跖角化症, 基因突变, 变异分类
Abstract:
Objective · To explore the main mutation types and pathogenicity of the coding region of keratin 9 gene (KRT9) in Chinese Han population, and to provide reference information for the classification and prediction of clinical diagnosis of the disease with epidermolytic palmoplantar keratoderma (EPPK). Methods · 834 subjects were recruited 278 families that were not affectedEPPK in the Chinese Han population. The mutations in the coding region of KRT9 gene were detectedusing the next-generation sequencing (NGS)-based gene panel combined with Sanger sequencing. The pathogenicity analysis of variants was performedusing SIFT and Polyphen-2 prediction software. Results · A total of twelve KRT9 gene mutations were detected in the Chinese Han population based on 834 individuals 278 families. Among the twelve different mutations, six synonymous mutations and six missense mutations were identified, respectively. The assessment of pathogenicity of KRT9 gene variants was analyzedbioinformatics tools, such as SIFT and Polyphen-2 prediction, conservative analysis, and database query. Furthermore, these missense mutations were classified as benign or possibly benign variants. Conclusion · In this study, six missense mutations in the coding region of KRT9 gene exon were detected in the Chinese Han population. According to the American Society of Medical Genetics and Genomics (ACMG) variant classification guide, all the six variants were benign or possibly benign. However, previous reports have found that a KRT9 c.1216T>C (p.C406R) mutation was pathogenic in a pedigree with EPPK, which were inconsistent with our findings, and the pathogenicity of this mutation still has to be verifiedfurther functional experiments.
Key words: KRT9 gene, epidermolytic palmoplantar keratoderma (EPPK), gene mutation, variant classification


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