Millat Gilles, Bouvagnet Patrice, Chevalier Philippe, Sebbag Laurent, Dulac Arnaud, Dauphin Claire, Jouk Pierre-Simon, Delrue Marie-Ange, Thambo Jean-Benoit, Le Metayer Philippe, Seronde Marie-France, Faivre Laurence, Eicher Jean-Christophe, Rousson Robert
Laboratoire de Cardiogénétique Moléculaire, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, Lyon, France.
Eur J Med Genet. 2011 Nov-Dec;54(6):e570-5. doi: 10.1016/j.ejmg.2011.07.005. Epub 2011 Aug 4.
Dilated Cardiomyopathy (DCM) is one of the leading causes of heart failure with high morbidity and mortality. More than 30 genes have been reported to cause DCM. To provide new insights into the pathophysiology of dilated cardiomyopathy, a mutational screening on 4 DCM-causing genes (MYH7, TNNT2, TNNI3 and LMNA) was performed in a cohort of 105 unrelated DCM (64 familial cases and 41 sporadic cases) using a High Resolution Melting (HRM)/sequencing strategy. Screening of a highly conserved arginine/serine (RS)-rich region in exon 9 of RBM20 was also performed. Nineteen different mutations were identified in 20 index patients (19%), including 10 novels. These included 8 LMNA variants in 9 (8.6%) probands, 5 TNNT2 variants in 5 probands (4.8%), 4 MYH7 variants in 3 probands (3.8%), 1 TNNI3 variant in 1 proband (0.9%), and 1 RBM20 variant in 1 proband (0.9%). One proband was double-heterozygous. LMNA mutations represent the most prevalent genetic DCM cause. Most patients carrying LMNA mutations exhibit conduction system defects and/or cardiac arrhythmias. Our study also showed than prevalence of mutations affecting TNNI3 or the (RS)-rich region of RBM20 is lower than 1%. The discovery of novel DCM mutations is crucial for clinical management of patients and their families because pre-symptomatic diagnosis is possible and precocious intervention could prevent or ameliorate the prognosis.
扩张型心肌病（DCM）是导致心力衰竭的主要原因之一，发病率和死亡率都很高。据报道，有30多个基因可导致DCM。为了深入了解扩张型心肌病的病理生理学，我们采用高分辨率熔解（HRM）/测序策略，对105例无亲缘关系的DCM患者（64例家族性病例和41例散发性病例）进行了4个致DCM基因（MYH7、TNNT2、TNNI3和LMNA）的突变筛查。我们还对RBM20外显子9中一个高度保守的富含精氨酸/丝氨酸（RS）的区域进行了筛查。在20例索引患者（19%）中鉴定出19种不同的突变，其中包括10种新突变。这些突变包括9例先证者（8.6%）中的8种LMNA变异、5例先证者（4.8%）中的5种TNNT2变异、3例先证者（3.8%）中的4种MYH7变异、1例先证者（0.9%）中的1种TNNI3变异和1例先证者（0.9%）中的1种RBM20变异。1例先证者为双杂合子。LMNA突变是最常见的遗传性DCM病因。大多数携带LMNA突变的患者表现出传导系统缺陷和/或心律失常。我们的研究还表明，影响TNNI3或RBM20富含RS区域的突变发生率低于1%。发现新的DCM突变对于患者及其家族的临床管理至关重要，因为可以进行症状前诊断，并且早期干预可以预防或改善预后。
