Rampersaud Evadnie, Siegfried Jill D, Norton Nadine, Li Duanxiang, Martin Eden, Hershberger Ray E
Miami Institute for Human Genomics, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
Prog Pediatr Cardiol. 2011 Jan 1;31(1):39-47. doi: 10.1016/j.ppedcard.2010.11.008.
Dilated cardiomyopathy (DCM) in infants and children can be partially explained by genetic cause but the catalogue of known genes is limited. We reviewed our database of 41 cases diagnosed with DCM before 18 years of age who underwent detailed clinical and genetic evaluation, and summarize here the evidence for mutations causing DCM in these cases from 15 genes (PSEN1, PSEN2, CSRP3, LBD3, MYH7, SCN5A, TCAP, TNNT2, LMNA, MYBPC3, MYH6, TNNC1, TNNI3, TPM1, and RBM20). Thirty-five of the 41 pediatric cases had relatives with adult-onset DCM. More males (66%) were found among children diagnosed after 1 year of age with DCM. Nineteen mutations in 9 genes were identified among 15 out of 41 patients; 3 patients (diagnosed at ages 2 weeks, 9 and 13 years) had multiple mutations. Of the 19 mutations identified in 12 families, mutations in TPM1 (32%) and TNNT2 (21%) were the most commonly found. Of the 6 patients diagnosed before 1 year of age, 3 had mutations in TPM1 (including a set of identical twins), 1 in TNNT2, 1 in MYH7, and 1 with multiple mutations (MYH7 and TNNC1). Most DCM was accompanied by advanced heart failure and need for cardiac transplantation. We conclude that in some cases pediatric DCM has a genetic basis, which is complicated by allelic and locus heterogeneity as seen in adult-onset DCM. We suggest that future prospective comprehensive family-based genetic studies of pediatric DCM are indicated to further define mutation frequencies in known genes and to discover novel genetic cause.
婴幼儿和儿童扩张型心肌病（DCM）部分可由遗传因素解释，但已知基因种类有限。我们回顾了数据库中41例18岁前诊断为DCM并接受详细临床和基因评估的病例，在此总结这些病例中15个基因（PSEN1、PSEN2、CSRP3、LBD3、MYH7、SCN5A、TCAP、TNNT2、LMNA、MYBPC3、MYH6、TNNC1、TNNI3、TPM1和RBM20）导致DCM的突变证据。41例儿科病例中有35例亲属患有成人期DCM。1岁后诊断为DCM的儿童中男性更多（66%）。41例患者中有15例鉴定出9个基因的19种突变；3例患者（分别在2周、9岁和13岁诊断）有多种突变。在12个家族鉴定出的19种突变中，TPM1（32%）和TNNT2（21%）的突变最为常见。在1岁前诊断的6例患者中，3例有TPM1突变（包括一对同卵双胞胎），1例有TNNT2突变，1例有MYH7突变，1例有多种突变（MYH7和TNNC1）。大多数DCM伴有晚期心力衰竭且需要心脏移植。我们得出结论，在某些情况下，儿科DCM有遗传基础，如同成人期DCM一样存在等位基因和位点异质性。我们建议未来开展基于家庭的儿科DCM前瞻性综合基因研究，以进一步明确已知基因的突变频率并发现新的遗传病因。
