Akademik Veri Yönetim Sistemi
Annual Meeting of the Peripheral-Nerve-Society (PNS), Montreal, Kanada, 22 - 25 Haziran 2024, cilt.29, ss.11, (Özet Bildiri)
Introduction: Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy. Owing to the advances in molecular genetics, the genetic landscape of CMT has evolved in recent years; however, data from under-represented populations in genetic studies remain limited. Methods: In this study, we describe the genetic and clinical features of patients with CMT at our department. Pathogenic variants were identified utilizing MLPA (multiplex ligation-dependent probe amplification), Sanger sequencing, and exome sequencing. Results: Overall, 310 patients from 264 families with definitive genetic diagnosis were included in this study. The most frequent subtype was CMT1 (135 families), followed by CMT4 (45 families), CMT-I (31 families), CMT2 (27 families), and AR-CMT2 (26 families). The most frequently mutated genes were PMP22, GJB1, MFN2, SH3TC2 and GDAP1, respectively. Interestingly, only eight families were identified with MPZ variants. Among 76 families with recessive subtypes, causative variants were identified in 20 different genes. We identified pathogenic or likely pathogenic variants in genes unusual for a predominantly CMT phenotype, including FXN, SPG7, and ATM. The mean age of onset was 13.68 ± 12.32 years (range 1-57), and 151 patients were female (48.7%). Patients with autosomal recessive CMT forms, have an early disease onset (mean: 6.28 ± 6.01, range 1-29 years). Symptoms related to lower limb weakness or skeletal deformities were the most common presenting complaint, followed by delayed motor milestones. Among patients with delayed motor milestones, 23 had an autosomal recessive CMT subtype. Atypical clinical features, such as cranial nerve involvement, were more frequent in recessive forms. Conclusions: Our study described the genetic distribution of CMT in a referral center in Türkiye by including the largest number of genetically solved cases to date. Furthermore, we expanded the genetic and phenotypic spectrum by identifying novel variants and describing new clinical features.