Identification of novel mutations in RBM20 in patients with dilated cardiomyopathy.
Identification of novel mutations in RBM20 in patients with dilated cardiomyopathy.
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在心肌病的患者中鉴定RBM20的新突变。
DOI：
10.1111/j.1752-8062.2010.00198.x
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发表时间：
2010-06
影响因子：
3.9
通讯作者：
Hershberger, Ray E.
中科院分区：
文献类型：
--
作者：
Li, Duanxiang;Morales, Ana;Gonzalez-Quintana, Jorge;Norton, Nadine;Siegfried, Jill D.;Hofmeyer, Mark;Hershberger, Ray E.
大多数扩张型心肌病(DCM)的遗传基础尚不清楚。最近的一项研究表明，编码核糖核酸结合蛋白的基因RBM20外显子9上一个高度定位的5个氨基酸热点的突变导致了侵袭性DCM。我们进行了这项研究，以确认和扩大在另一个扩张型心肌病队列中RBM20突变的性质。临床心血管数据、家族史和血液样本收集自特发性扩张型心肌病患者。对312个DCM先证者的DNA进行了测序，以检测RBM20基因第6至9外显子的核苷酸变化，以及尽可能多的家族成员。我们在6个无关先证者中发现了6个独特的RBM20罕见变异(1.9%)。在外显子6的5个氨基酸的热点区域发现了4个突变，其中2个是新发现的(R634W，R636C)，2个是已知的(R634Q，R636H)，另外两个新的突变(外显子6的V535I和外显子9的R716Q)不在该热点之外。起病年龄和心力衰竭的严重程度各不相同，心律失常和传导系统缺陷也是如此，但许多受试者患有严重的心力衰竭，导致早期死亡或心脏移植。RBM20突变患者中的扩张型心肌病与晚期疾病相关。
The genetic basis of most of dilated cardiomyopathy (DCM) cases remains unknown. A recent study indicated that mutations in a highly localized 5 amino acid hotspot in exon 9 of RBM20, a gene encoding a ribonucleic acid binding protein, caused aggressive DCM. We undertook this study to confirm and extend the nature of RBM20 mutations in another DCM cohort. Clinical cardiovascular data, family histories, and blood samples were collected from patients with idiopathic DCM. DNA from 312 DCM probands were sequenced for nucleotide alterations in exons 6 through 9 of RBM20, and additional family members as possible. We found six unique RBM20 rare variants in six unrelated probands (1.9%). Four mutations, two of which were novel (R634W, R636C) and two previously identified (R634Q, R636H), were identified in a 5 amino acid hotspot in exon 6. Two other novel variants (V535I in exon 6, R716Q in exon 9) were outside of this hotspot. Age of onset and severity of heart failure were variable, as were arrhythmias and conduction system defects, but many subjects suffered severe heart failure resulting in early death or cardiac transplantation. Dilated cardiomyopathy in patients with RBM20 mutations is associated with advanced disease.
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DOI：
10.1016/s0735-1097(99)00276-4
发表时间：
1999-09-01
影响因子：
24
作者：
Crispell, KA;Wray, A;Hershberger, RE
通讯作者：
Hershberger, RE
影响因子：
9.8
作者：
Li, Duanxiang;Parks, Sharie B.;Hershberger, Ray E.
通讯作者：
Hershberger, Ray E.
DOI：
10.1016/s0735-1097(02)01788-6
发表时间：
2002-05-01
影响因子：
24
作者：
Crispell, KA;Hanson, EL;Hershberger, RE
通讯作者：
Hershberger, RE
影响因子：
3.9
作者：
Hershberger, Ray E.;Parks, Sharie B.;Litt, Michael
通讯作者：
Litt, Michael
影响因子：
37.8
作者：
Vasan, RS;Larson, MG;Benjamin, EJ
通讯作者：
Benjamin, EJ