Evaluating the Genetic Subtypes and Phenotypic Features of Charcot-Marie-Tooth Disease in Türkiye
Fatma Yesim Parman1, Arman Cakar1, Ayse Candayan2, Gulandam Bagırova3, Zehra Oya Uyguner3, Serdar Ceylaner4, Hacer Durmus1, Esra Battaloglu5
1Neuromuscular Unit, Istanbul University, Istanbul Faculty of Medicine, 2Molecular Genomics Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium and Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium, 3Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, 4Medical Genetics, Intergen Genetics Laboratory, Ankara, Turkey, 5Department of Molecular Biology and Genetics, Bogazici University, İstanbul, Türkiye
Objective:
To describe the clinical and genetic characteristics of patients with Charcot-Marie-Tooth disease (CMT) in Turkey.
Background:
CMT is the most common inherited neuromuscular disorder. Although the genetic landscape of the disease has evolved in recent years, current knowledge chiefly comes from Europe and North America.
Design/Methods:
We evaluated the clinical and genetic features of 327 patients from 280 families with CMT who were followed at the Neuromuscular Unit of the Istanbul Faculty of Medicine, Istanbul University.
Results:
The mean age of onset was 13.38 ± 12.45 years (range 1-57), and 159 patients were female (48.7%). Patients with autosomal recessive CMT forms have an early disease onset (mean: 6.15 ± 6.20, range 1-29 years). Lower limb weakness or skeletal deformities were the most frequent presenting complaints. Cranial nerve involvement and other unusual features were more frequent in autosomal recessive forms. The most frequent subtype was CMT1 (138 families), followed by CMT4 (49 families), CMT-I (33 families), AR-CMT2 (31 families), and CMT2 (29 families). The most frequently mutated genes were PMP22, GJB1, MFN2, SH3TC2, and GDAP1, respectively. On the other hand, only ten families were identified with MPZ variants. Among 85 families with recessive subtypes, causative variants were identified in 22 different genes. We identified pathogenic or likely pathogenic variants in genes unusual for a predominantly CMT phenotype, including SPG7, NDUFS6, FXN, and ATM.
Conclusions:
Our study provided an update on the genetic landscape of CMT in Türkiye. We expanded the genetic and phenotypic spectrum by identifying novel variants and describing new clinical features. Compared to previous studies, the frequency of rare autosomal recessive subtypes was significantly higher in our cohort.
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