Cakar Arman, Candayan Ayse, Bagırova Gulandam, Uyguner Zehra Oya, Ceylaner Serdar, Durmus Hacer, Battaloglu Esra, Parman Yesim
Neuromuscular Unit, Neurology Department, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Department of Molecular Biology and Genetics, Bogazici University, Istanbul, Turkey.
Eur J Neurol. 2025 Jan;32(1):e16572. doi: 10.1111/ene.16572.
Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy. In this study, we aimed to analyze the genetic spectrum and describe phenotypic features in a large cohort from Türkiye.
Demographic and clinical findings were recorded. Patients were initially screened for PMP22 duplication. Targeted sequencing or whole-exome sequencing was performed in duplication-negative patients.
Overall, 311 patients from 265 families were included. Demyelinating CMT (67.4%) was more common than axonal (20.5%) and intermediate subtypes (11.7%). PMP22 duplication was the most frequent mutation, followed by pathogenic variants in GJB1, MFN2, SH3TC2, and GDAP1 genes. MPZ-neuropathy was rare in our cohort (3.0%). Interestingly, CMT4 is the second most common type after CMT1. Lower extremity weakness and foot deformities were the most frequent presenting complaints. Striking clinical features included a high frequency of scoliosis in SH3TC2, peripheral hyperexcitability in HINT1, and central nervous system findings in GJB1. Autosomal recessive CMT subtypes had higher CMTESv2 scores when compared to autosomal dominant ones (12.39 ± 4.81 vs. 8.36 ± 4.15, p: 0.023). Twenty-one patients used wheelchairs during their last examination. Among them, 16 had an autosomal recessive subtype. Causative variants were identified in 31 genes, including 28 novel pathogenic or likely pathogenic changes.
Our findings provided robust data regarding the genetic distribution of CMT in Türkiye, which may pave the path for building population-specific diagnostic gene panels. Rare autosomal recessive subtypes were relatively frequent in our cohort. By analyzing genotype-phenotype correlations, our data may provide clinical clues for clinicians.
夏科-马里-图斯（CMT）病是最常见的遗传性神经病。在本研究中，我们旨在分析土耳其一个大型队列中的基因谱并描述表型特征。
记录人口统计学和临床发现。最初对患者进行PMP22重复筛查。对重复阴性的患者进行靶向测序或全外显子组测序。
总共纳入了来自265个家庭的311名患者。脱髓鞘型CMT（67.4%）比轴索性（20.5%）和中间型亚型（11.7%）更常见。PMP22重复是最常见的突变，其次是GJB1、MFN2、SH3TC2和GDAP1基因中的致病变异。MPZ神经病在我们的队列中很少见（3.0%）。有趣的是，CMT4是仅次于CMT1的第二常见类型。下肢无力和足部畸形是最常见的主诉。显著的临床特征包括SH3TC2中脊柱侧弯的高发生率、HINT1中外周兴奋性增高以及GJB1中的中枢神经系统表现。与常染色体显性CMT亚型相比，常染色体隐性CMT亚型的CMTESv2评分更高（12.39±4.81对8.36±4.15，p：0.023）。21名患者在最后一次检查时使用轮椅。其中，16名患有常染色体隐性亚型。在31个基因中鉴定出致病变异，包括28个新的致病或可能致病的变化。
我们的研究结果提供了关于土耳其CMT基因分布的有力数据，这可能为构建针对特定人群的诊断基因panel铺平道路。罕见的常染色体隐性亚型在我们的队列中相对常见。通过分析基因型-表型相关性，我们的数据可能为临床医生提供临床线索。
