Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Animal Biology Dept, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Neurogenetics. 2024 Nov 27;26(1):11. doi: 10.1007/s10048-024-00790-8.
We present a 7.5-year-old boy born to a family from the Iranian Azeri Turkish ethnic group with a consanguineous marriage who presents with a unique set of symptoms, suggesting Giant Axonal Neuropathy. He achieved independent walking at age 3 years, with frequent falling during running. Physical and neurological examinations reveal curly blond hair, generalized muscle atrophy, slow speech and difficulty swallowing solid food, foot drop, pes cavus, hammertoe deformities; reduced deep tendon reflexes, clumsy gait, impaired sense of position, and intention tremors.This comprehensive report significantly expands the clinical and mutational spectrum of Giant Axonal Neuropathy. Whole Exome Sequencing (WES) analysis revealed a novel homozygous variant (NC_000016.10(NM_022041.3):c.2T > C) in the GAN gene, confirmed by Sanger sequencing. Segregation analysis showed that the parents were heterozygous for the variant. The variant was absent in a cohort of 430 healthy individuals from the same ethnic group and in other published population databases such as GenomAD and the 1000 Genome. The clinical manifestations, segregation analysis, population study, and bioinformatics analysis collectively confirm the pathogenicity of variant.
我们介绍了一名 7.5 岁男孩，他出生于一个伊朗阿塞拜疆土耳其族裔的近亲家庭，具有独特的一系列症状，提示为巨轴索神经病。他 3 岁时能够独立行走，但在跑步时经常摔倒。体格检查和神经系统检查显示卷曲的金发、全身肌肉萎缩、言语缓慢和吞咽固体食物困难、足下垂、高弓足、槌状趾畸形；深腱反射减弱、步态笨拙、位置感和意向性震颤受损。本综合报告显著扩展了巨轴索神经病的临床和突变谱。外显子组测序（WES）分析显示 GAN 基因中的一个新的纯合变异（NC_000016.10（NM_022041.3）：c.2T>C），经 Sanger 测序证实。家系分析显示，父母均为该变异的杂合子。该变异在来自同一族群的 430 名健康个体的队列中以及在其他已发表的人群数据库（如 GenomAD 和 1000 基因组）中均不存在。临床表现、家系分析、人群研究和生物信息学分析共同证实了变异的致病性。
