主页 > 医学讨论 >
【文摘发布】儿童与成人心脏肥大的共同遗传起
Hiroyuki Morita, M.D., Heidi L. Rehm, Ph.D., Andres Menesses, M.D., Barbara McDonough, R.N., Amy E. Roberts, M.D., Raju Kucherlapati, Ph.D., Jeffrey A. Towbin, M.D., J.G. Seidman, Ph.D., and Christine E. Seidman, M.D.
ABSTRACT
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<0.005). Neither hypertrophic severity nor contractile function correlated with familial or genetic status. Cardiac transplantation and sudden death were more prevalent among mutation-positive than among mutation-negative children; implantable cardioverter–defibrillators were more frequent (P=0.007) in children with family histories that were positive for the mutation.
Conclusions Genetic causes account for about half of presumed sporadic cases and nearly two thirds of familial cases of childhood-onset hypertrophy. Childhood-onset hypertrophy should prompt genetic analyses and family evaluations.
全文点击：
http://content.nejm.org/cgi/content/full/358/18/1899 Shared Genetic Causes of Cardiac Hypertrophy in Children and Adults
儿童和成人肥厚性心肌病的共同的遗传基础
Hiroyuki Morita, M.D., Heidi L. Rehm, Ph.D., Andres Menesses, M.D., Barbara McDonough, R.N., Amy E. Roberts, M.D., Raju Kucherlapati, Ph.D., Jeffrey A. Towbin, M.D., J.G. Seidman, Ph.D., and Christine E. Seidman, M.D.
ABSTRACT
摘要
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.
背景： 儿童时期特发性肥厚性心肌病无心肌病家族病史，预示着预后不良。尽管形态上与成年遗传心肌疾病相似，但基因是否导致儿童初发型肥厚，这是未知的。
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.
评估方法：我们的评估了年龄未满15岁（均数[±标准差]年龄，6.99 ± 6.12岁）诊断为特发性心肌肥厚性心肌病的84名儿童（63个男孩和21个女孩）的家庭史和医疗史。我们进行了以下8个基因测序： myh7 ， mybpc3 ， tnnt2 ， tnni3 ， tpm1 ， myl3 ， myl2 ， actc 。这些基因编码的肌节蛋白质，当其突变时会导致成人心肌疾病。我们还测序prkag2和lamp2 ，其编码代谢蛋白质;这些基因突变可导致早发性心室肥厚。
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<0.005). Neither hypertrophic severity nor contractile function correlated with familial or genetic status. Cardiac transplantation and sudden death were more prevalent among mutation-positive than among mutation-negative children; implantable cardioverter–defibrillators were more frequent (P=0.007) in children with family histories that were positive for the mutation.
阅读本文的人还阅读：
作者:admin@医学,生命科学 2010-10-14 17:11
医学,生命科学网