Identification of two novel mutations in the ventricular regulatory myosin light chain gene (MYL2) associated with familial and classical forms of hypertrophic cardiomyopathy
Identification of two novel mutations in the ventricular regulatory myosin light chain gene (MYL2) associated with familial and classical forms of hypertrophic cardiomyopathy
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DOI：
10.1007/s001090050210
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发表时间：
1998-03-01
影响因子：
4.7
通讯作者：
Hainque, B
中科院分区：
文献类型：
--
作者：
Flavigny, J;Richard, P;Hainque, B
自1989年以来，已经确定了与家族性和经典型肥厚性心肌病相关的5个编码肉瘤蛋白的疾病基因。1996年，另外两个编码心室调节和必需肌球蛋白轻链的基因被证明与以左心室中部梗阻为特征的疾病的特定表型相关。本研究的目的是寻找心室调节肌球蛋白轻链基因（MYL2）的突变，该基因位于染色体12q23q24.3上，在一组42个先证中呈现典型的家族性肥厚性心肌病表型。利用单链构象多态性分析寻找MYL2基因编码段的突变，并对异常产物进行测序。两个新的错义突变。外显子2的Phe18Leu和外显子4的Arg58Gln在三个不相关的家族中被发现。所有受影响的患者均未出现仅局限于乳头肌水平的肥厚，并伴有左心室中部梗阻。通过基因重组分析。在一个大家庭中发现的这些突变之一使我们能够在遗传图谱上完善MYL2基因的定位。在6厘米的间隔内含有6个信息丰富的微卫星标记。总之，我们表明MYL2基因突变可能与家族性和经典形式的肥厚性心肌病有关，我们为家族性肥厚性心肌病患者的遗传分析提供了新的工具。
Five disease genes encoding sarcomeric proteins and associated with familial and classical forms of hypertrophic cardiomyopathy have been determined since 1989, In 1996 two other genes encoding ventricular regulatory and essential myosin light chains were shown to be associated with a particular phenotype of the disease characterized by mid left ventricular obstruction. The aim of the present study was to search for mutations in the ventricular regulatory myosin light chain gene (MYL2), located on chromosome 12q23q24.3, in a panel of 42 probands presenting a classical phenotype of familial hypertrophic cardiomyopathy. Single-strand conformation polymorphism analysis was used to search for mutations in the coding segments of the MYL2 gene, and the abnormal products were sequenced. Two novel missense mutations. Phe18Leu in exon 2 and Arg58Gln in exon 4 were identified in three unrelated families. None of the affected patients had hypertrophy localized only at the level of the papillary muscle with mid left ventricular obstruction. By analysis of genetic recombinations. one of these mutations identified in a large family allowed us to refine the localization of the MYL2 gene on the genetic map. in an interval of 6 cM containing six informative microsatellite markers. In conclusion, we show that mutations in the MYL2 gene may be involved in familial and classical forms of hypertrophic cardiomyopathy, and we provide new tools for the genetic analysis of patients with familial hypertrophic cardiomyopathy.