Abdallah Atiyeh M, Carlus S Justin, Al-Mazroea Abdulhadi H, Alluqmani Mohammad, Almohammadi Yousef, Bhuiyan Zahurul A, Al-Harbi Khalid M
West Midlands Regional Genetics Laboratory, The Birmingham Women's and Children's NHS Foundation Trus, B15 2TT Birmingham, UK.
Cardiogenetics Unit, Pediatrics Department, College of Medicine, Taibah University, 30001 Al-Madinah, Saudi Arabia.
Medicina (Kaunas). 2019 Jan 15;55(1):17. doi: 10.3390/medicina55010017.
: Dilated cardiomyopathy (DCM) is a rare cardiac disease characterised by left ventricular enlargement, reduced left ventricular contractility, and impaired systolic function. Childhood DCM is clinically and genetically heterogenous and associated with mutations in over 100 genes. The aim of this study was to identify novel variations associated with infantile DCM. : Targeted next generation sequencing (NGS) of 181 cardiomyopathy-related genes was performed in three unrelated consanguineous families from Saudi Arabia. Variants were confirmed and their frequency established in 50 known DCM cases and 80 clinically annotated healthy controls. : The three index cases presented between 7 and 10 months of age with severe DCM. In Family A, there was digenic inheritance of two heterozygous variants: a novel variant in (c.3925G > A, p.Asp1309Asn) and a known DCM mutation in (c.2770G > A; p.Glu924Lys). The p.Asp1309Asn variant was predicted to be likely pathogenic according to international guidelines. The other two families had no identifiable potentially deleterious variants. : Inheritance of two genetic variants may have a synergistic or dose effect to cause severe DCM. We report of a novel p.Asp1309Asn variation associated with DCM. Targeted NGS is useful in the molecular diagnosis of DCM and to guide whole-family management and counselling.
扩张型心肌病（DCM）是一种罕见的心脏疾病，其特征为左心室扩大、左心室收缩力降低以及收缩功能受损。儿童期DCM在临床和遗传方面具有异质性，与100多个基因的突变相关。本研究的目的是鉴定与婴儿期DCM相关的新变异。：对来自沙特阿拉伯的三个无血缘关系的近亲家庭中的181个与心肌病相关的基因进行了靶向二代测序（NGS）。在50例已知DCM病例和80例经临床注释的健康对照中对变异进行了确认并确定了其频率。：这三名先证者在7至10个月大时出现严重DCM。在A家族中，存在两个杂合变异的双基因遗传：一个在 中的新变异（c.3925G > A，p.Asp1309Asn）和一个在 中的已知DCM突变（c.2770G > A；p.Glu924Lys）。根据国际指南， p.Asp1309Asn变异预计可能具有致病性。另外两个家族未发现可识别的潜在有害变异。：两个遗传变异的遗传可能具有协同或剂量效应，从而导致严重DCM。我们报告了一个与DCM相关的新的p.Asp1309Asn变异。靶向NGS在DCM的分子诊断以及指导全家族管理和咨询方面很有用。
