Digenic mutational inheritance of the integrin alpha 7 and the myosin heavy chain 7B genes causes congenital myopathy with left ventricular non-compact cardiomyopathy.
Digenic mutational inheritance of the integrin alpha 7 and the myosin heavy chain 7B genes causes congenital myopathy with left ventricular non-compact cardiomyopathy.
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DOI：
10.1186/1750-1172-8-91
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发表时间：
2013-06-21
影响因子：
3.7
通讯作者：
Di Iorio G
中科院分区：
文献类型：
--
作者：
Esposito T;Sampaolo S;Limongelli G;Varone A;Formicola D;Diodato D;Farina O;Napolitano F;Pacileo G;Gianfrancesco F;Di Iorio G
我们报告了一个意大利家庭，其中先证者表现出严重的表型，其特征是先天性纤维型失调（CFTD）与左心室非压实性心肌病（LVNC）相关。本研究的重点是鉴定负责基因/s。利用全外显子组测序方法，我们发现了肌球蛋白重链7B （MYH7B）和整合素- 7 （ITGA7）两个基因的先证纯合错义突变。这两种基因都在心脏和肌肉组织中表达，这两种突变都被认为是有害的，在健康人群中没有发现。MYH7B基因R890C突变分离为LVNC表型。在一名与LVNC无关的患者中也发现了它，证实了它在心肌病中的致病作用。ITGA7基因（肌肉纤维基底层的关键成分）的E882K突变仅在先证者中发现，这表明它在CFTD中起作用。这项研究确定了两个新的疾病基因。MYH7B突变导致典型的LVNC表型，而ITGA7突变导致CFTD。这两种表型都代表骨骼肌和心肌成熟的改变，通常不严重。先证者的严重表型很可能是由于这两个突变的协同作用。这项研究为孟德尔性状的遗传学基础提供了新的见解，并证明了基因遗传在复杂表型中的作用。
We report an Italian family in which the proband showed a severe phenotype characterized by the association of congenital fiber type disproportion (CFTD) with a left ventricular non-compaction cardiomyopathy (LVNC). This study was focused on the identification of the responsible gene/s. Using the whole-exome sequencing approach, we identified the proband homozygous missense mutations in two genes, the myosin heavy chain 7B (MYH7B) and the integrin alpha 7 (ITGA7). Both genes are expressed in heart and muscle tissues, and both mutations were predicted to be deleterious and were not found in the healthy population. The R890C mutation in the MYH7B gene segregated with the LVNC phenotype in the examined family. It was also found in one unrelated patient affected by LVNC, confirming a causative role in cardiomyopathy. The E882K mutation in the ITGA7 gene, a key component of the basal lamina of muscle fibers, was found only in the proband, suggesting a role in CFTD. This study identifies two novel disease genes. Mutation in MYH7B causes a classical LVNC phenotype, whereas mutation in ITGA7 causes CFTD. Both phenotypes represent alterations of skeletal and cardiac muscle maturation and are usually not severe. The severe phenotype of the proband is most likely due to a synergic effect of these two mutations. This study provides new insights into the genetics underlying Mendelian traits and demonstrates a role for digenic inheritance in complex phenotypes.
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DOI：
10.1093/jnen/62.10.977
发表时间：
2003-10-01
影响因子：
3.2
作者：
Clarke, NF;North, KN
通讯作者：
North, KN
影响因子：
11.2
作者：
Laing, NG;Clarke, NF;Nonaka, I
通讯作者：
Nonaka, I
影响因子：
3.9
作者：
Lawlor, Michael W.;DeChene, Elizabeth T.;Roumm, Emily;Geggel, Amelia S.;Moghadaszadeh, Behzad;Beggs, Alan H.
通讯作者：
Beggs, Alan H.
影响因子：
6.1
作者：
Esposito, Teresa;Rendina, Domenico;Strazzullo, Pasquale
通讯作者：
Strazzullo, Pasquale
影响因子：
2.8
作者：
Hermida-Prieto, M;Monserrat, L;Crespo-Leiro, M
通讯作者：
Crespo-Leiro, M