KRT5基因新突变(p.Gly207Asp)导致一家系伴斑状色素沉着的单纯性大疱性表皮松解症

A novel p.Gly207Asp mutation responsible for epidermolysis bullosa simplex with mottled pigmentation in a single Chinese family

目的:对伴斑状色素沉着的单纯性大疱性表皮松解症一家系进行KRT5和KRT14致病基因突变筛查。方法:提取家系中每一位成员的DNA样本,应用聚合酶链式反应(PCR)扩增KRT5和KRT14基因编码区及外显子-内含子交界区,对PCR产物进行DNA测序。选择100例正常人群作为对照组,将突变结果在The Genome Aggregation Database(gnomAD)和The Exome Aggregation Consortium(ExAC)等多个大样本数据库中查询突变频率。结果:该家系中KRT14基因检测未发现异常;KRT5基因在先证者中检测到1个未报道的错义突变c.620G>A(p.Gly207Asp),患儿父亲及弟弟均检测到该突变。该家系中该突变和表型共分离,该突变c.620G>A(p.Gly207Asp)在GenBank及人类基因突变数据库(HGMD)等国际数据库中尚未见报道。结论:KRT5基因全新点突变c.620G>A(p.Gly207Asp),可能是引起该家系中伴斑状色素沉着的单纯性大疱性表皮松解症患儿发病的原因。

Objective:To investigate the mutations of all coding exons and exon-intron boundaries of KRT5 gene and KRT14 gene in the proband and other members of epidermolysis bullosa simplex with mottled pigmentation(EBS-MP) in a single Chinese family. Methods:All coding exons and exon-intron boundaries of KRT5 gene and KRT14 gene were amplified through PCR. The PCR products were sequenced. The DNA samples from 100 normal subjects were also sequenced for control. Mutation frequency of results were researched in the Genome Aggregation Database(gnomAD), the Exome Aggregation Consortium(ExAC) and other large sample databases. Results:KRT14 gene was normal in the family members. The novel mutation of KRT5 gene, c.620 G>A(p.Gly207 Asp), was detected in the proband. The mutation was positive in his father and brother. The mutation and phenotype were co-segregated in the family. So far, the missense mutation(p.Gly207 Asp) was not reported in international databases, including GenBank and HGMD databases. Conclusion:As a new point mutation of KRT5 gene, c.620 G>A(p.Gly207 Asp) may be the cause of epidermolysis bullosa simplex patient with mottled pigmentation.