泛发性雀斑样痣三例SASH1基因突变研究

Study on SASH1 genetic mutations in 3 patients of generalized lentiginosis

目的研究3例临床诊断为泛发性雀斑样痣患者的基因突变情况,以进一步明确诊断和为家系提供遗传咨询。方法收集3例先证者及父母的临床资料,提取外周血基因组DNA,对先证者行全外显子组测序,Sanger测序验证全外显子测序结果及父母相应位点变异情况。结果3例先证者检出SASH1基因3种杂合变异,分别为c.15261527insAAGT(p.Leu511Lysfs*21),c.1520C>T(p.Ser507Phe)和c.1761C>G(p.Ser587Arg),致病性分级分别为致病变异和可能致病变异。其中,c.1520C>T(p.Ser507Phe)为文献未见报道的新变异。结论结合临床表型和基因检测结果,3例先证者均确诊为泛发性雀斑样痣。新变异的鉴定,丰富了人类基因突变数据库,为泛发性雀斑样痣的基因诊断和遗传咨询提供了有益信息。

Objective In order to provide evidence for diagnosis and genetic counseling,genetic analysis was performed on three patients that clinically diagnosed as generalized lentiginosis.Methods Genomic DNA was extracted from peripheral blood of the three probands and their parents.Whole exome sequencing was carried out on the three probands.Sanger sequencing was further used to identify the sequencing results and the causative genes among the available family members.Results Three heterozygotes variations were detected in the three probands,c.15261527 insAAGT(p.Leu511 Lysfs*21),c.1520 C>T(p.Ser507 Phe)and c.1761 C>G(p.Ser587 Arg),which were classified as pathogenic variation and likely pathogenic variation.Among them,c.1520 C>T(p.ser507 phe)was a novel variation which had not been reported.Conclusion According to the clinical phenotype and gene test results,all the three probands were diagnosed as generalized lentiginosis.The findings of our study expand the mutational database in humans and provide important information for the genetic diagnosis and genetic counseling of generalized lentiginosis.