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.
■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。