A novel 5bp deletion in HPS4 gene associates with Hermansky-Pudlak Syndrome

Hermansky-Pudlak Syndrome (HPS) is a rare autosomal recessive lysosomal storage disorder characterized by oculocutaneous albinism, bleeding diathesis and in some cases pulmonary fibrosis, granulomatous colitis. While genetic alterations in HPS genes are known to cause the disorder, we explored genetic variations associated with HPS in an individual with clinical manifestations of HPS. We present a 58-year-old female patient from Southern India, born to consanguineous parents, who presented with clinical features of HPS. Whole-exome sequencing (WES) was performed, followed by Sanger sequencing to validate the specific genetic variation in the proband and available family members. WES analysis identified a novel homozygous 5bp deletion variant in the HPS4 gene (c.838_842del; p.Ser280ProfsTer34) in the proband. Familial genetic screening by Sanger sequencing confirmed the homozygous pathogenic variant in the proband and a heterozygous pathogenic variant in her family members. The identified pathogenic variant from this study emphasizes the importance of genetic analysis for accurate clinical diagnosis, management, and genetic diversity of HPS. To the best of our knowledge, this novel variant identified in the HPS4 gene causing Hermansky-Pudlak Syndrome is the first report deletion variant from the Indian population. Our findings will facilitate genetic counseling of the affected family and reduce the disease burden in future generations.