目的 采用全外显子组测序鉴定1个常染色体隐性遗传白化病家系患者的致病基因,探讨其发病机制.方法 采集先证者及其家系成员外周血并提取其基因组DNA,对先证者进行全基因外显子组测序,并结合序列变异生物信息学分析方法,鉴定其致病基因,利用Sanger测序对基因突变位点验证.结果 全外显子组测序结果显示,先证者HPS1基因存在由c.1276_1279dupGGAG(p.Asp427fs)移码突变和c.398+5G>A剪切位点变异组成的复合杂合突变,而其表型正常的父亲为c.1276_1279dupGGAG(p.Asp427fs)杂合突变,表型正常的母亲为c.398+5G>A杂合突变.结论 该白化病先证者由HPS1基因c.1276_1279dupGGAG和c.398+5G>A复合杂合突变导致,此患者被诊断为Hermansky-Pudlak综合征1型.外显子测序技术可以快速准确地筛查白化病候选基因,并明确其具体临床亚型,有利于临床医师积极干预患者潜在并发症以及改善患者生存质量.%Objective In this study,whole exome sequencing was used to identify disease-causing genes for a pedigree with autosomal recessive albinism and pathogenesis mechanism. Methods Genomic DNA was extracted from peripheral blood samples of proband and other family members. Whole exome sequencing was performed for proband. The disease-causing mutations were determined by whole exome sequencing with sequence variation bioinformatics analysis,and the mutations were identified by Sanger sequencing. Results Proband was diagnosed with compound heterozygous mutations in HPS1 gene,including c.1276_1279dupGGAG (p.Asp427fs) mutation and c.398+5G>A mutation. The frameshifting mutation was inherited from father,and the splicing mutation was inherited from mother. Conclusions The compound heterozygous c.1276_1279dupGGAG and c.398+5G>A mutations of HPS1 gene are identified as causative mutations for albinism in this family. The proband is diagnosed as Hermansky-Pudlak syndrome 1 subtype. The whole exome sequencing can be a new and efficient method to determine specific disease gene and subtype in albinism,and it can improve the treatment and patients' live quality.
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