Hu Xuyun, Guo Ruolan, Qi Zhan, Zhang Yingzi, Li Wei, Hao Chanjuan
Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China; Henan Key Laboratory of Inherited Metabolic Diseases, Pediatric Research Institute of Zhengzhou Children's Hospital, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, Henan 450053, China.
Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
Clin Chim Acta. 2024 Jul 15;561:119813. doi: 10.1016/j.cca.2024.119813. Epub 2024 Jun 12.
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.
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.
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.
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.
Hermansky-Pudlak综合征（HPS）是一种罕见的常染色体隐性遗传病，伴有多种临床表现，包括眼皮肤白化病、出血倾向和全身并发症。早期准确诊断对于医疗干预和遗传咨询至关重要。我们旨在通过对新生儿进行基因筛查，来确定中国人群中HPS致病基因变异的患病率和谱。
使用下一代测序技术对来自13个省份的29622名中国新生儿进行HPS突变的基因筛查。根据美国医学遗传学与基因组学学会（ACMG）指南鉴定并分类致病基因变异。估计患病率，并确定潜在的热点变异。
在筛查的新生儿中，鉴定出215名携带103种不同致病基因变异的携带者，其中两名携带者还有额外的错义变异。在7个基因中鉴定出潜在的热点变异，这些变异在各自基因的携带者中总共占比超过20%。特别是，HPS3基因c.1838C>G变异仅在中国人群中被报道，提示可能存在奠基者效应。中国HPS的估计患病率为2.84/1000000。
我们的研究为中国人群中HPS的遗传格局提供了有价值的见解，有助于遗传咨询、早期诊断和管理策略。这些发现有助于加强对中国HPS的理解和管理。
