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Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
摘要：
■肥厚型心肌病（HCM）是最常见的遗传性心脏病，具有明显的遗传和临床异质性。最近,杂合ALPK3截短变体(ALPK3tv)已显示引起HCM。然而,ALPK3变异谱及其与中国HCM患者临床特征的关系尚待阐明.
■来自986例HCM患者和761例无HCM对照的全外显子组测序数据用于分析ALPK3变异。在18例HCM患者中检测到11例ALPK3tv（1.8％），而在对照中未发现此类变异。我们还在16例HCM患者（1.6％）和8例对照（1.1％）中检测到21例罕见的ALPK3错义变异，分别。ALPK3tv在HCM患者中显著富集(P<0.001),而错义变异的患病率在HCM组和对照组之间具有可比性(P=0.309).ALPK3tv患者的左心室流出道梯度明显较低（P=0.011），心尖型HCM患病率较高（27.8%；P=0.008）。
■我们的研究支持杂合ALPK3tv，但不是APLK3错觉变体，是HCM的遗传原因。携带ALPK3tv的HCM患者发展根尖HCM的可能性更大。
■来自986例HCM患者和761例无HCM对照的全外显子组测序数据用于分析ALPK3变异。在18例HCM患者中检测到11例ALPK3tv（1.8％），而在对照中未发现此类变异。我们还在16例HCM患者（1.6％）和8例对照（1.1％）中检测到21例罕见的ALPK3错义变异，分别。ALPK3tv在HCM患者中显著富集(P<0.001),而错义变异的患病率在HCM组和对照组之间具有可比性(P=0.309).ALPK3tv患者的左心室流出道梯度明显较低（P=0.011），心尖型HCM患病率较高（27.8%；P=0.008）。
■我们的研究支持杂合ALPK3tv，但不是APLK3错觉变体，是HCM的遗传原因。携带ALPK3tv的HCM患者发展根尖HCM的可能性更大。
