Ataxia Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.
Department of Paediatrics, Division of Paediatric Neurology, Growth and Development Research Center, Children's Medical Centre, Paediatrics Centre of Excellence, Tehran University of Medical Sciences, Tehran, Iran.
Mol Genet Genomic Med. 2023 Jun;11(6):e2159. doi: 10.1002/mgg3.2159. Epub 2023 Mar 3.
Giant axonal neuropathy (GAN) is a progressive childhood hereditary polyneuropathy that affects both the peripheral and central nervous systems. Disease-causing variants in the gigaxonin gene (GAN) cause autosomal recessive giant axonal neuropathy. Facial weakness, nystagmus, scoliosis, kinky or curly hair, pyramidal and cerebellar signs, and sensory and motor axonal neuropathy are the main symptoms of this disorder. Here, we report two novel variants in the GAN gene from two unrelated Iranian families.
Clinical and imaging data of patients were recorded and evaluated, retrospectively. Whole-exome sequencing (WES) was undertaken in order to detect disease-causing variants in participants. Confirmation of a causative variant in all three patients and their parents was carried out using Sanger sequencing and segregation analysis. In addition, for comparing to our cases, we reviewed all relevant clinical data of previously published cases of GAN between the years 2013-2020.
Three patients from two unrelated families were included. Using WES, we identified a novel nonsense variant [NM_022041.3:c.1162del (p.Leu388Ter)], in a 7-year-old boy of family 1, and a likely pathogenic missense variant [NM_022041.3:c.370T>A (p.Phe124Ile)], in two affected siblings of the family 2. Clinical examination revealed typical features of GAN-1 in all three patients, including walking difficulties, ataxic gait, kinky hair, sensory-motor polyneuropathy, and nonspecific neuroimaging abnormalities. Review of 63 previously reported cases of GAN indicated unique kinky hair, gait problem, hyporeflexia/areflexia, and sensory impairment were the most commonly reported clinical features.
One homozygous nonsense variant and one homozygous missense variant in the GAN gene were discovered for the first time in two unrelated Iranian families that expand the mutation spectrum of GAN. Imaging findings are nonspecific, but the electrophysiological study in addition to history is helpful to achieve the diagnosis. The molecular test confirms the diagnosis.
巨轴索神经病（GAN）是一种进行性儿童遗传性多神经病，影响周围和中枢神经系统。Gigaxonin 基因（GAN）的致病变异导致常染色体隐性遗传巨轴索神经病。面部无力、眼球震颤、脊柱侧凸、卷发或曲发、锥体束和小脑征以及感觉和运动轴索神经病是这种疾病的主要症状。在这里，我们报告了来自两个不相关的伊朗家庭的 GAN 基因中的两个新变异。
记录和评估患者的临床和影像学数据，回顾性研究。对参与者进行全外显子组测序（WES）以检测致病变异。通过 Sanger 测序和分离分析，对所有三名患者及其父母进行了所有三个患者的致病变异的确认。此外，为了与我们的病例进行比较，我们回顾了 2013 年至 2020 年期间发表的所有关于 GAN 的相关临床数据。
两个不相关家庭的 3 名患者被纳入研究。使用 WES，我们在家族 1 的 7 岁男孩中发现了一个新的无义变异 [NM_022041.3：c.1162del（p.Leu388Ter)]，在家族 2 的两名受影响的兄弟姐妹中发现了一个可能的致病性错义变异 [NM_022041.3：c.370T>A（p.Phe124Ile)]。所有三名患者的临床检查均显示出 GAN-1 的典型特征，包括行走困难、共济失调步态、卷发、感觉运动多发性神经病和非特异性神经影像学异常。对 63 例先前报道的 GAN 病例的回顾表明，独特的卷发、步态问题、反射减退/消失和感觉障碍是最常见的临床特征。
在两个不相关的伊朗家庭中，首次发现 GAN 基因中的一个纯合无义变异和一个纯合错义变异，扩展了 GAN 的突变谱。影像学发现是非特异性的，但除了病史之外，电生理学研究有助于做出诊断。分子测试可确认诊断。
