Discovery of a potentially deleterious variant in TMEM87B in a patient with a hemizygous 2q13 microdeletion suggests a recessive condition characterized by congenital heart disease and restrictive cardiomyopathy.
Discovery of a potentially deleterious variant in TMEM87B in a patient with a hemizygous 2q13 microdeletion suggests a recessive condition characterized by congenital heart disease and restrictive cardiomyopathy.
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在 2q13 半合子微缺失患者的 TMEM87B 中发现潜在有害变异，提示其患有以先天性心脏病和限制性心肌病为特征的隐性病症。
DOI：
10.1101/mcs.a000844
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发表时间：
2016
影响因子：
1.8
通讯作者：
Shaikh,TamimH
中科院分区：
文献类型：
--
作者：
Yu,Hung-Chun;Coughlin,CurtisR;Geiger,ElizabethA;Salvador,BlakeJ;Elias,EllenR;Cavanaugh,JeanL;Chatfield,KathrynC;Miyamoto,ShelleyD;Shaikh,TamimH
限制性心肌病（RCM）是一种罕见的心肌疾病，在心肌病类型中死亡率最高。RCM的病因学知之甚少，虽然遗传原因已被牵连，和综合征协会已被描述。在这里，我们描述了一个病人与房间隔缺损和限制性心肌病沿着随着颅面畸形和智力残疾。使用染色体微阵列分析（CMA）的初步筛选确定了母系遗传的2q13微缺失。该患者具有许多以前报告的复发性2q13微缺失综合征病例的特征。然而，未受影响的母亲的微缺失的遗传结合低发病率（10%）和轻度形式的心脏缺陷在以前的报告的情况下，CMA结果的临床意义尚不清楚。进行了全外显子组测序（WES）和基于trio的分析，并确定了一个父系遗传的TMEM87B突变（c.1366A>G，p.Asn456Asp）的患者。TMEM87 B是一种高度保守的跨膜蛋白，目前功能未知，位于复发性2q13微缺失综合征的关键区域。此外，最近的一项研究表明，斑马鱼胚胎中TMEM 87 B的缺失影响心脏发育，导致心脏发育不全。因此，通过结合CMA和WES，我们潜在地发现了一种常染色体隐性遗传疾病，其特征在于由TMEM87 B突变引起的严重心脏表型。本研究扩大了与复发性2q13微缺失综合征相关的表型谱，也进一步表明了TMEM 87在其病因学，特别是心脏病理学中的作用。
Restrictive cardiomyopathy (RCM) is a rare cause of heart muscle disease with the highest mortality rate among cardiomyopathy types. The etiology of RCM is poorly understood, although genetic causes have been implicated, and syndromic associations have been described. Here, we describe a patient with an atrial septal defect and restrictive cardiomyopathy along with craniofacial anomalies and intellectual disabilities. Initial screening using chromosomal microarray analysis (CMA) identified a maternally inherited 2q13 microdeletion. The patient had many of the features reported in previous cases with the recurrent 2q13 microdeletion syndrome. However, the inheritance of the microdeletion from an unaffected mother combined with the low incidence (10%) and milder forms of cardiac defects in previously reported cases made the clinical significance of the CMA results unclear. Whole-exome sequencing (WES) with trio-based analysis was performed and identified a paternally inheritedTMEM87Bmutation (c.1366A>G, p.Asn456Asp) in the patient. TMEM87B, a highly conserved, transmembrane protein of currently unknown function, lies within the critical region of the recurrent 2q13 microdeletion syndrome. Furthermore, a recent study had demonstrated that depletion of TMEM87B in zebrafish embryos affected cardiac development and led to cardiac hypoplasia. Thus, by combining CMA and WES, we potentially uncover an autosomal-recessive disorder characterized by a severe cardiac phenotype caused by mutations inTMEM87B. This study expands the spectrum of phenotypes associated with the recurrent 2q13 microdeletion syndrome and also further suggests the role ofTMEM87Bin its etiology, especially the cardiac pathology.