Genetic screening reveals hotspot variants and prevalence rates of Hermansky-Pudlak syndrome in the Chinese population.

ABSTRACT

BACKGROUND: Hermansky-Pudlak Syndrome (HPS) is a rare autosomal recessive genetic disorder associated with varied clinical manifestations, including oculocutaneous albinism, bleeding tendency, and systemic complications. Early and accurate diagnosis is crucial for medical interventions and genetic counseling. We aimed to characterize the prevalence and spectrum of pathogenic variants of HPS in the Chinese population through genetic screening of newborns. METHODS: Genetic screening for HPS mutations was conducted in 29,622 Chinese newborns from 13 provinces using next-generation sequencing. Pathogenic variants were identified and classified according to ACMG guidelines. Prevalence rates were estimated, and potential hotspot variants were identified. RESULTS: Among screened newborns, 215 carriers with 103 distinct pathogenic variants were identified, including two carriers with additional missense variants. Potential hotspot variants in seven genes were identified, collectively representing over 20 % of carriers in each respective gene. Particularly, the HPS3 c.1838C>G variant was exclusively reported in the Chinese population, suggesting a potential founder effect. The estimated prevalence rate of HPS in China was 2.84/1,000,000. CONCLUSION: Our study provides valuable insights into the genetic landscape of HPS in the Chinese population, aiding in genetic counseling, early diagnosis, and management strategies. These findings contribute to enhancing the understanding and management of HPS in China.