Pediatric Cardiomyopathy: New Insight Into Potential Disease Mechanisms.
Pediatric Cardiomyopathy: New Insight Into Potential Disease Mechanisms.
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小儿心肌病：对潜在疾病机制的新见解。
DOI：
10.1016/j.jacc.2015.11.030
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发表时间：
2016
影响因子：
24
通讯作者：
Taylor,MatthewRG
中科院分区：
文献类型：
--
作者：
Mestroni,Luisa;Sweet,MaryE;Taylor,MatthewRG
心肌病是一种临床异质性疾病，损害心脏功能。虽然心肌病可以发生在任何年龄，但儿科心肌病的年发病率特别高，每10万名18岁以下儿童中有1.13例，每10万名婴儿中有8.34例（1）。小儿心肌病有遗传和非遗传原因。儿科人群中心肌病的遗传病因比成人人群更多样化，因为它们不仅包括成人中描述的大多数心肌病基因，还包括其他综合征，代谢和神经肌肉遗传原因。基因检测的广泛应用使小儿心肌病的诊断率从30%提高到76%（2）。然而，近25%的病例仍是特发性的，原因不明，可能是遗传。(3)报告ALPK3作为一个新的基因在人类小儿心肌病。使用纯合性作图，全外显子组测序和候选基因筛选的组合，该小组确定了ALPK3中的纯合提前终止密码子突变，并从心脏组织的免疫组织学观察中提出了进一步探索的潜在机制。首先，进行纯合性作图，
Cardiomyopathies are clinically heterogeneous disorders that impair heart function. Although cardiomyopathies can occur at any age, pediatric cardiomyopathies in particular have an annual incidence of 1.13 cases in 100,000 children younger than 18 years of age and 8.34 cases per 100,000 infants (1). Pediatric cardiomyopathies have both genetic and nongenetic causes. Genetic etiologies of cardiomyopathy in the pediatric population are more diverse than the adult population because they encompass not only a majority of the cardiomyopathy genes described in adults, but additional syndromic, metabolic, and neuromuscular genetic causes as well. Expanded use of genetic testing has increased the diagnostic yield from w30% to 76% of pediatric cardiomyopathy cases (2). Nevertheless, nearly 25% of cases remain idiopathic with unknown, possibly genetic, causes.In this issue of the Journal, Almomani et al.(3) report ALPK3 as a novel gene in human pediatric cardiomyopathy. Using a combination of homozygosity mapping, whole exome sequencing, and candidate gene screening, the group identified homozygous premature stop codon mutations in ALPK3 and, from immunohistological observations of heart tissue, suggest potential mechanisms for further exploration. First, homozygosity mapping was