Center for Personalized Medicine, Children's Hospital, Los Angeles, 2100 West 3rd St, Los Angeles, CA, 90057, USA; Division of Genomic Medicine, Department of Pathology, Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA, 90027, USA.
Department of Neurology, Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA, 90027, USA.
Eur J Med Genet. 2021 Jan;64(1):104121. doi: 10.1016/j.ejmg.2020.104121. Epub 2020 Dec 8.
The EEF1A2 gene encodes eukaryotic translation elongation factor 1α2, an integral component of the elongation factor complex. Heterozygous pathogenic variants in EEF1A2 are associated with neurodevelopmental disorders characterized by epilepsy, global developmental delay, and autism. To date, dilated cardiomyopathy has only been reported in two siblings with neurodevelopmental phenotypes and a homozygous missense variant in EEF1A2. This report describes a nine-year-old female patient who presented with neurodevelopmental phenotypes and dilated cardiomyopathy. Analysis of 193 epilepsy genes by focused exome sequencing revealed a novel heterozygous variant c.46G > C (p.Val16Leu; NM_001958.3) in EEF1A2. The variant was not detected in either parent, confirming its de novo origin. No additional variants that explain the patient's phenotypes were found by subsequent whole exome analysis. Copy number analysis of the exome data and exon-level microarray excluded a deletion in the other allele of EEF1A2. We present the first patient with a heterozygous pathogenic EEF1A2 variant who had dilated cardiomyopathy as well as neurodevelopmental phenotypes, suggesting that this cardiac phenotype may be associated with the autosomal dominant form of the EEF1A2-related disorder.
EEF1A2 基因编码真核翻译延伸因子 1α2,是延伸因子复合物的一个组成部分。EEF1A2 中的杂合致病性变异与以癫痫、全面发育迟缓以及自闭症为特征的神经发育障碍有关。迄今为止,只有在具有神经发育表型的两名同胞和 EEF1A2 的纯合错义变异中才报道过扩张型心肌病。本报告描述了一名 9 岁女性患者,其表现为神经发育表型和扩张型心肌病。通过靶向外显子组测序对 193 个癫痫基因进行分析,发现 EEF1A2 中存在一个新的杂合变异 c.46G>C(p.Val16Leu; NM_001958.3)。该变异在父母双方均未检出,证实其为新生突变。随后的全外显子分析未发现可解释患者表型的其他变异。外显子组数据的拷贝数分析和外显子水平微阵列排除了 EEF1A2 另一个等位基因的缺失。我们报告了首例携带 EEF1A2 致病性杂合变异的患者,其患有扩张型心肌病和神经发育表型,表明这种心脏表型可能与 EEF1A2 相关疾病的常染色体显性形式有关。