İpek Rojan, Çavdartepe Büşra Eser, Bozdoğan Sevcan Tuğ, Altunışık Erman, Akalın Akçahan, Yaman Mahmut, Akın Alper, Kumandaş Sefer
Department of Pediatric Neurology, Dicle University, Diyarbakır 21280, Türkiye.
Department of Medical Genetics, Konya City Hospital, Konya 42020, Türkiye.
Genes (Basel). 2025 Jul 30;16(8):917. doi: 10.3390/genes16080917.
Charcot-Marie-Tooth disease (CMT) is a genetically and phenotypically heterogeneous hereditary neuropathy. Axonal CMT type 2 (CMT2) subtypes often exhibit overlapping clinical features, which makes molecular genetic analysis essential for accurate diagnosis and subtype differentiation. This retrospective study included five pediatric patients who presented with gait disturbance, muscle weakness, and foot deformities and were subsequently diagnosed with axonal forms of CMT. Clinical data, electrophysiological studies, neuroimaging, and genetic analyses were evaluated. Whole exome sequencing (WES) was performed in three sporadic cases, while targeted CMT gene panel testing was used for two siblings. Variants were interpreted using ACMG guidelines, supported by public databases (ClinVar, HGMD, and VarSome), and confirmed by Sanger sequencing when available. All had absent deep tendon reflexes and distal muscle weakness; three had intellectual disability. One patient was found to carry a novel homozygous frameshift variant (c.2568_2569del) in the gene, consistent with CMT2S. Other variants were identified in the (CMT2CC), (CMT2O), and (CMT2EE) genes. Notably, a previously unreported co-occurrence of mutation and congenital heart disease was observed in one case. This study expands the clinical and genetic spectrum of pediatric axonal CMT and highlights the role of early physical examination and molecular diagnostics in detecting rare variants. Identification of a novel variant and unique phenotypic associations provides new insights for future genotype-phenotype correlation studies.
夏科-马里-图思病（CMT）是一种遗传和表型均具有异质性的遗传性神经病。轴索性2型CMT（CMT2）亚型通常表现出重叠的临床特征，这使得分子遗传学分析对于准确诊断和亚型区分至关重要。这项回顾性研究纳入了5例表现为步态障碍、肌肉无力和足部畸形的儿科患者，随后被诊断为轴索性CMT。对临床数据、电生理研究、神经影像学和基因分析进行了评估。对3例散发病例进行了全外显子组测序（WES），而对2例同胞使用了靶向CMT基因panel检测。变异体根据美国医学遗传学与基因组学学会（ACMG）指南进行解读，公共数据库（ClinVar、HGMD和VarSome）提供支持，如有可能则通过桑格测序进行确认。所有患者均无深部腱反射且远端肌肉无力；3例有智力障碍。发现1例患者在 基因中携带一种新的纯合移码变异（c.2568_2569del），符合CMT2S。在 （CMT2CC）、 （CMT2O）和 （CMT2EE）基因中鉴定出其他变异体。值得注意的是，在1例病例中观察到一种先前未报告的 突变与先天性心脏病的共现情况。本研究扩展了儿科轴索性CMT的临床和遗传谱，并强调了早期体格检查和分子诊断在检测罕见变异体中的作用。鉴定出一种新的 变异体和独特的表型关联为未来的基因型-表型相关性研究提供了新的见解。
