Abstract：
Biallelic disease-causing variants in the ALPK3 gene were first identified in children presenting with a severe cardiomyopathy. More recently, it was shown that carriers of heterozygous ALPK3 null variants are at risk of developing hypertrophic cardiomyopathy (HCM) with an adult onset. Since the number of reported ALPK3 patients is small, the mutational spectrum and clinical data are not fully described. In this multi-centric study, we described the molecular and clinical spectrum of a large cohort of ALPK3 patients. Genetic testing using targeted next generation sequencing was performed in 16 183 cardiomyopathy index cases. Thirty-six patients carried at least one null ALPK3 variant. The five paediatric patients carried two ALPK3 variants, all presented an HCM phenotype with severe outcomes (one transplantation, one heart failure and one cardiac arrest). The 31 adult patients carried heterozygous variants and the main phenotype was HCM (n = 26/31); including 15% (n = 4) presented with an apical or a concentric form of hypertrophy. Reporting a large cohort of ALPK3 patients, this collaborative work confirmed a strong association with HCM and suggesting his screening in the context of idiopathic HCM.
摘要：
首先在患有严重心肌病的儿童中发现了ALPK3基因中引起双等位基因疾病的变异。最近,研究表明,杂合子ALPK3无效变异体的携带者在成年后有发展为肥厚型心肌病(HCM)的风险.由于报告的ALPK3患者数量很少，突变谱和临床数据尚未完全描述.在这项多中心研究中，我们描述了大量ALPK3患者的分子和临床谱.在16183例心肌病指数病例中进行了使用靶向下一代测序的基因检测。36名患者携带至少一个无效的ALPK3变体。五名儿科患者携带两种ALPK3变体，全部呈现HCM表型，结果严重(一次移植，一次心力衰竭和一次心脏骤停)。31名成年患者携带杂合变体，主要表型为HCM（n=26/31）；包括15％（n=4）的顶端或同心形式的肥大。报告了大量ALPK3患者，这项合作研究证实了与HCM的强烈关联,并建议他在特发性HCM的背景下进行筛查.
