Abstract:

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.

Key words: HPS1 gene, Albinism, Hermansky-Pudlak syndrome 1 subtype, Whole exome sequencing