Spectrum and genotype–phenotype relationship of ALPK3 variants in Chinese patients with hypertrophic cardiomyopathy
Jing Wang,
Fang Wang,
Guixin Wu,
Minjie Lu,
Channa Zhang,
Lei Song,
Yibing Shao,
Jizheng Wang,
Fusong Liu,
Mei Zhang
Affiliations
Jing Wang
Department of Cardiology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China; Department of Cardiology, Qingdao Municipal Hospital, Qingdao, 266071, Shandong, China
Fang Wang
Department of Cardiology, The Third People's Hospital of Qingdao City, Qingdao, 266041, Shandong, China
Guixin Wu
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China; Cardiomyopathy Ward, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
Minjie Lu
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
Channa Zhang
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
Lei Song
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China; Cardiomyopathy Ward, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China; National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
Yibing Shao
Department of Cardiology, Qingdao Municipal Hospital, Qingdao, 266071, Shandong, China
Jizheng Wang
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China; Corresponding author.
Fusong Liu
Department of Cardiology, The Third People's Hospital of Qingdao City, Qingdao, 266041, Shandong, China; Corresponding author.
Mei Zhang
Department of Cardiology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China; Corresponding author.
Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease, and it has obvious genetic and clinical heterogeneity. Recently, heterozygous ALPK3 truncating variants (ALPK3tv) have been shown to cause HCM. However, the spectrum of ALPK3 variants and their relationships with the clinical characteristics of Chinese patients with HCM remain to be elucidated. Methods and results: Whole-exome sequencing data from 986 patients with HCM and 761 controls without HCM were utilized to analyze ALPK3 variants. Eleven ALPK3tv were detected in 18 patients with HCM (1.8 %), while no such variants were identified in controls. We also detected 21 rare ALPK3 missense variants in 16 patients with HCM (1.6 %) and 8 controls (1.1 %), respectively. ALPK3tv were significantly enriched in patients with HCM (P < 0.001), whereas the prevalence of missense variants was comparable between the HCM and control groups (P = 0.309). Patients with ALPK3tv exhibited a significantly lower left ventricular outflow tract gradient (P = 0.011) and a higher prevalence of apical HCM (27.8 %; P = 0.008). Conclusions: Our study supports that heterozygous ALPK3tv, but not APLK3 missense variants, are a genetic cause of HCM. Patients with HCM carrying ALPK3tv have a greater likelihood of developing apical HCM.
