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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：Hermansky-Pudlak综合征（HPS）是一种罕见的常染色体隐性遗传障碍，与多种临床表现相关，包括眼皮肤白化病，出血倾向,和全身性并发症。早期和准确的诊断对于医学干预和遗传咨询至关重要。我们旨在通过新生儿的遗传筛查来表征中国人群中HPS致病变异的患病率和谱。
方法：使用下一代测序技术，对来自13个省的29,622名中国新生儿进行了HPS突变的遗传筛查。根据ACMG指南鉴定和分类病原变异。估计了患病率，并确定了潜在的热点变体。
结果：在筛查的新生儿中，215个携带者与103个不同的致病变种被鉴定，包括两个带有其他错义变体的运营商。确定了七个基因的潜在热点变异，共同代表每个基因中超过20%的携带者。特别是,HPS3c.1838C>G变异只在中国人群中报道，暗示潜在的创始人效应。HPS在中国的患病率估计为2.84/1,000,000。
结论：我们的研究为中国人群HPS的遗传景观提供了有价值的见解，协助遗传咨询,早期诊断,和管理策略。这些发现有助于提高中国对HPS的理解和管理。
方法：使用下一代测序技术，对来自13个省的29,622名中国新生儿进行了HPS突变的遗传筛查。根据ACMG指南鉴定和分类病原变异。估计了患病率，并确定了潜在的热点变体。
结果：在筛查的新生儿中，215个携带者与103个不同的致病变种被鉴定，包括两个带有其他错义变体的运营商。确定了七个基因的潜在热点变异，共同代表每个基因中超过20%的携带者。特别是,HPS3c.1838C>G变异只在中国人群中报道，暗示潜在的创始人效应。HPS在中国的患病率估计为2.84/1,000,000。
结论：我们的研究为中国人群HPS的遗传景观提供了有价值的见解，协助遗传咨询,早期诊断,和管理策略。这些发现有助于提高中国对HPS的理解和管理。
