Shinwari Zarghuna M A, Almesned Abdulrahman, Alakhfash Ali, Al-Rashdan Ahmad M, Faqeih Eissa, Al-Humaidi Zainab, Alomrani Ahmed, Alghamdi Malak, Colak Dilek, Alwadai Abdullah, Rababh Monther, Al-Fayyadh Majid, Al-Hassnan Zuhair N
Prince Sultan Cardiac Center, Qassim, Saudi Arabia.
Cardiology. 2017;137(3):188-192. doi: 10.1159/000465516. Epub 2017 Apr 26.
Cardiomyopathy (CMP) in children is a clinically and genetically heterogeneous group of disorders. Disease-associated mutations have been identified in more than 50 genes. Recently, mutations in the mitochondrial tRNA processing gene, ELAC2, were reported to be associated with the recessively inherited form of hypertrophic CMP (HCM). This study is aimed at describing the cardiac phenotype and outcome of ELAC2 mutation.
We performed whole exome sequencing followed by targeted mutation screening to identify the genetic etiology of severe infantile-onset CMP in 64 consanguineous Saudi families.
A previously reported mutation (p.Phe154Leu) in ELAC2 gene was detected in 16 families. The index cases presented between 2 and 7 months of age with HCM in 13 infants and dilated CMP (DCM) in 3. Pericardial effusion was observed in 7 infants (44%). All infants died with a median age of death of 4 months. Almost 1/3 of them died during the initial presentation.
Our study suggests screening the ELAC2 gene in severe infantile-onset HCM or DCM of unknown etiology, especially in the presence of pericardial effusion. Our work demonstrates a universally poor outcome of the (p.Phe154Leu) variant in ELAC2 gene; a correlation that helps in counseling parents and in planning appropriate medical intervention.
儿童心肌病（CMP）是一组临床和遗传异质性疾病。已在50多个基因中鉴定出与疾病相关的突变。最近，据报道线粒体tRNA加工基因ELAC2中的突变与肥厚型CMP（HCM）的隐性遗传形式有关。本研究旨在描述ELAC2突变的心脏表型和预后。
我们进行了全外显子组测序，随后进行靶向突变筛查，以确定64个沙特近亲家庭中严重婴儿期起病的CMP的遗传病因。
在16个家庭中检测到ELAC2基因中一个先前报道的突变（p.Phe154Leu）。索引病例在2至7个月龄时出现，13例婴儿患有HCM，3例患有扩张型CMP（DCM）。7例婴儿（44%）观察到心包积液。所有婴儿均死亡，中位死亡年龄为4个月。其中近1/3在初次就诊时死亡。
我们的研究建议对病因不明的严重婴儿期起病的HCM或DCM进行ELAC2基因筛查，尤其是在心包积液存在的情况下。我们的工作证明了ELAC2基因中（p.Phe154Leu）变异的普遍不良预后；这种相关性有助于为父母提供咨询并规划适当的医疗干预。
