Familial dilated cardiomyopathy and isolated left ventricular noncompaction associated with lamin A/C gene mutations
Familial dilated cardiomyopathy and isolated left ventricular noncompaction associated with lamin A/C gene mutations
复制标题
DOI：
10.1016/j.amjcard.2004.03.029
复制
发表时间：
2004-07-01
影响因子：
2.8
通讯作者：
Crespo-Leiro, M
中科院分区：
文献类型：
--
作者：
Hermida-Prieto, M;Monserrat, L;Crespo-Leiro, M
LMNA突变与伴有或不伴有传导系统疾病的家族性或散发性扩张型心肌病(DC)有关。我们研究了67例DC患者的LMNA基因(其中18例为家族性DC，17例可能为家族性DC，32例为散发性DC)。从基因组DNA中，用聚合酶链式反应扩增LMNA基因编码区，单链构象多态性分析，循环测序。用限制性内切酶片段长度多态方法证实基因突变。在A和B家族中发现了两个致病突变。在A家族中，母亲和她的同卵双胞胎女儿中存在一种新的R349L突变。他们在36岁、18岁和20岁时接受了心脏移植。在B家系中，2名无传导系统疾病的DC表亲(1名45岁接受心脏移植手术，1名46岁猝死)及其2名儿子均存在R190W突变。两名受影响患者的母亲在40多岁时死于心脏原因(我突然死亡)。其中一名携带者符合孤立性左心室致密化不全的诊断标准。我们的数据将LMNA的R349L和R190W突变与严重形式的家族性DC联系在一起。在无传导系统疾病的家族性DC患者的基因筛查中应考虑LMNA突变。孤立性左心室致密化不全可能是椎板病变表型谱的一部分。(C)2004年，由Excerpta Medica，Inc.
LMNA mutations have been associated with familial or sporadic dilated cardiomyopothy (DC) with or without conduction system disease. We studied the LMNA gene in 67 consecutive patients with DC (18 had familial DC, 17 had possible familial DC, and 32 sporadic DC). From genomic DNA, coding regions of the LMNA gene were amplified by polymerase chain reaction, studied by single-strand conformation polymorphism, and cycle sequenced. Mutations were confirmed by restriction fragment length polymorphism. Two disease-causing mutations were found in families A and B. In family A, a novel R349L mutation was present in the mother and her identical twin daughters. They required cardiac transplantation at 36, 18, and 20 years of age. In family B, the R190W mutation was present in 2 cousins with DC and without conduction system disease (1 had cardiac transplantation at 45 years of age and 1 died suddenly at 46 years of age) and in 2 of their sons. The mothers of the 2 affected patients died due to cardiac causes in their 40s (I died suddenly). One of the carriers fulfilled diagnostic criteria for isolated left ventricular noncompaction. Our data associated the R349L and R190W mutations in LMNA with severe forms of familial DC. LMNA mutations should be considered in the genetic screening of patients With familial DC without conduction system disease. Isolated left ventricular noncompaction may be part of the phenotypic spectrum of the laminopathies. (C) 2004 by Excerpta Medica, Inc.