Shared genetic causes of cardiac hypertrophy in children and adults
Shared genetic causes of cardiac hypertrophy in children and adults
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DOI：
10.1056/nejmoa075463
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发表时间：
2008-05-01
影响因子：
158.5
通讯作者：
Seidman, Christine E.
中科院分区：
文献类型：
--
作者：
Morita, Hiroyuki;Rehm, Heidi L.;Seidman, Christine E.
背景：儿童期发病的特发性心脏肥厚，如果没有心肌病家族史，可能预示预后不良。尽管形态学与成年期的遗传性心肌病相似，但遗传学对儿童期心肌肥大的影响尚不清楚。方法：我们评估了84例15岁前诊断为特发性心脏肥厚的儿童（男孩63例，女孩21例）的家族史和病史（平均[+/-SD]年龄，6.99+/-6.12岁）。我们测序了8个基因：MYH7、MYBPC3、TNNT2、TNNI3、TPM1、MYL3、MYL2和ACTC。这些基因编码的肌瘤蛋白一旦发生突变，就会引起成人心肌病。我们还对编码代谢蛋白的PRKAG2和LAMP2进行了测序；这些基因的突变可引起早发性心室肥厚。结果：我们在51例无心肌病家族史的患儿中发现了25例突变，在33例家族性心肌病患儿中发现了21例突变。在推定为散发疾病的25名儿童中的11名中，4名携带了新的突变，7名遗传了突变。突变主要发生在MYH7和MYBPC3（占儿童总数的75%）；MYBPC3错义突变明显多于成人发病的心肌病(P
Background: The childhood onset of idiopathic cardiac hypertrophy that occurs without a family history of cardiomyopathy can portend a poor prognosis. Despite morphologic similarities to genetic cardiomyopathies of adulthood, the contribution of genetics to childhood-onset hypertrophy is unknown.Methods: We assessed the family and medical histories of 84 children (63 boys and 21 girls) with idiopathic cardiac hypertrophy diagnosed before 15 years of age (mean [+/-SD] age, 6.99+/-6.12 years). We sequenced eight genes: MYH7, MYBPC3, TNNT2, TNNI3, TPM1, MYL3, MYL2, and ACTC. These genes encode sarcomere proteins that, when mutated, cause adult-onset cardiomyopathies. We also sequenced PRKAG2 and LAMP2, which encode metabolic proteins; mutations in these genes can cause early-onset ventricular hypertrophy.Results: We identified mutations in 25 of 51 affected children without family histories of cardiomyopathy and in 21 of 33 affected children with familial cardiomyopathy. Among 11 of the 25 children with presumed sporadic disease, 4 carried new mutations and 7 inherited the mutations. Mutations occurred predominantly (in >75% of the children) in MYH7 and MYBPC3; significantly more MYBPC3 missense mutations were detected than occur in adult-onset cardiomyopathy (P