Rezaei Zahra, Hosseinpour Sareh, Ashrafi Mahmoud Reza, Mahdieh Nejat, Alizadeh Houman, Mohammadpour Masoud, Khosroshahi Nahideh, Amanat Man, Tavasoli Ali Reza
Division of Pediatric Neurology, Children's Medical Center, Tehran University of Medical Sciences, Myelin Disorders Clinic, Tehran, Iran.
Faculty of Medicine, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
Neuropediatrics. 2019 Apr;50(2):130-134. doi: 10.1055/s-0039-1679911. Epub 2019 Feb 21.
Leukodystrophies are heterogeneous group of genetic white matter disorders with a wide range of neurologic and systemic manifestations. Defects in genes encoding aminoacyl tRNA (transfer ribonucleic acid) synthetase enzymes (aaRSs) are recently identified as the etiology of some leukodystrophies. Herein, we described two unrelated children referred to Children's Medical Center, Tehran, Iran, with developmental delay, nystagmus, seizures, psuedo-bulbar palsy and dystonia. Whole exome sequencing (WES) in both patients identified a homozygous (c.2T > C) variant in exon one of gene, encoding cytoplasmic arginyl-tRNA synthetase. Our finding was confirmed by segregation analysis. In silico analyses of the c.2T > C variant showed its possible pathogenic role due to the absence of the start codon. Severe hypomyelination was the common neuroimaging finding of both cases. Spinal cord involvement was found in one of our patients which was not previously reported in studies. We, therefore, showed that -related hypomyelination might affect spinal cord.
脑白质营养不良是一组异质性的遗传性白质疾病，具有广泛的神经和全身表现。编码氨酰tRNA（转移核糖核酸）合成酶（aaRSs）的基因缺陷最近被确定为某些脑白质营养不良的病因。在此，我们描述了两名转诊至伊朗德黑兰儿童医学中心的不相关儿童，他们有发育迟缓、眼球震颤、癫痫、假性延髓麻痹和肌张力障碍。两名患者的全外显子组测序（WES）均在编码细胞质精氨酰tRNA合成酶的基因外显子1中鉴定出纯合（c.2T>C）变异。我们的发现通过分离分析得到证实。对c.2T>C变异的计算机分析表明，由于起始密码子缺失，其可能具有致病作用。严重髓鞘形成不足是两例患者共同的神经影像学表现。我们的一名患者发现有脊髓受累，此前的研究中未报道过。因此，我们表明，相关的髓鞘形成不足可能会影响脊髓。
