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Should Identifying a Titin Truncating Variant Change the Management of Patients With Dilated Cardiomyopathy? ∗
Journal of the American College of Cardiology ( IF 21.7 ) Pub Date : 2017-10-01 , DOI: 10.1016/j.jacc.2017.09.020
Christopher Newton-Cheh

D ilated cardiomyopathy (DCM) is a major cause of morbidity and mortality with a prevalence estimated between 1 in 2500 and 1 in 250 (1). Although diverse clinical risk factors have been identified, roughly one-half of cases are idiopathic (2). A genetic basis is inferred from studies demonstrating familial aggregation and mutations in genes encoding over a dozen sarcomeric, structural, and nuclear envelope proteins have been identified in patients with sporadic and familial DCM. Screening of the first-degree family members of probands with idiopathic DCM with a history, electrocardiogram, and echocardiogram is recommended, but that approach is variably pursued. Identification of a pathogenic mutation in an affected DCM proband can facilitate molecular screening of family members and in a minority of cases may meaningfully affect the management of the proband (e.g., laminopathies secondary to mutations in LMNA). A substantial contribution to the genetic burden of DCM by truncating mutations in titin has recently been recognized (3). Titin is the largest human protein, extending from the Z-line to the M-line of the sarcomere, contributing passive force as well as altered calcium sensitivity in active tension. Rare coding variants in TTN were initially reported in 2002 in Native American and Japanese families with DCM (4,5). Titin is

中文翻译:

识别肌联蛋白截断变异是否应该改变扩张型心肌病患者的管理?*

扩张型心肌病 (DCM) 是发病率和死亡率的主要原因,其患病率估计在 2500 分之一到 250 分之一之间 (1)。尽管已经确定了多种临床风险因素,但大约一半的病例是特发性的 (2)。遗传基础是从表明家族聚集和编码十几种肌节、结构和核包膜蛋白的基因突变的研究中推断出来的,这些蛋白在散发性和家族性 DCM 患者中已被鉴定。建议对具有病史、心电图和超声心动图的特发性 DCM 先证者的一级家庭成员进行筛查,但这种方法的追求各不相同。在受影响的 DCM 先证者中识别致病突变可以促进对家庭成员的分子筛查,并且在少数情况下可能会对先证者的治疗产生有意义的影响(例如,继发于 LMNA 突变的椎板病)。最近已经认识到通过截断肌联蛋白中的突变对 DCM 的遗传负担有重大贡献 (3)。Titin 是最大的人类蛋白质,从肌节的 Z 线延伸到 M 线,有助于被动力以及主动张力下钙敏感性的改变。TTN 中罕见的编码变异最初于 2002 年在患有 DCM 的美洲原住民和日本家庭中报道 (4,5)。提丁是 最近已经认识到通过截断肌联蛋白中的突变对 DCM 的遗传负担有重大贡献 (3)。Titin 是最大的人类蛋白质,从肌节的 Z 线延伸到 M 线,有助于被动力以及主动张力下钙敏感性的改变。TTN 中罕见的编码变异最初于 2002 年在患有 DCM 的美洲原住民和日本家庭中报道 (4,5)。提丁是 最近已经认识到通过截断肌联蛋白中的突变对 DCM 的遗传负担有重大贡献 (3)。Titin 是最大的人类蛋白质,从肌节的 Z 线延伸到 M 线,有助于被动力以及主动张力下钙敏感性的改变。TTN 中罕见的编码变异最初于 2002 年在患有 DCM 的美洲原住民和日本家庭中报道 (4,5)。提丁是
更新日期:2017-10-01
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