Clinical and Genetic Features in X-Linked Charcot-Marie-Tooth Neuropathy (CMT-X) Patients from Turkey (P1.451)

Objective: The genetic heterogeneity in Charcot-Marie-Tooth (CMT) is a challenge for genetic diagnostics. Clinical clues and frequencies of mutations in CMT genes from large cohorts may help to develop strategies for efficient genetic testing. Background: The main cause of X-linked CMT is mutations in GJB1, also known as Connexin 32 (CMT-X). CMT-X is characterized by a moderate to severe motor and sensory neuropathy in affected males and usually milder symptoms carrier females. Design/Methods: Clinical, electrophysiological and genetic findings of 23 patients from 21 unrelated families diagnosed with CMT-1X at the Department of Neurology, Istanbul Faculty of Medicine between 1990 and 2017 were retrospectively evaluated. GJB1 mutation analyses were performed using direct Sanger sequencing after polymerase chain reaction (PCR) in 11 patients, whereas 5 patients were screened using Multiplex Amplification of Specific Targets for Resequencing (MASTR) assay and subsequent Sanger sequencing. Results: Nineteen patients were male. Mean age of onset in males was 11.7±5.5 (ranges 3–29) years and 27.7±1.7 (ranges 26–30) years in females. Slowly progressive weakness and atrophy of distal muscles in the feet (20/23) were the most common presenting symptoms. Two patients were presented with cramps in lower legs, and one patient with weakness in the hand. Only one patient had distal upper extremity dominant weakness, distal lower extremity weakness was more severe in others. Three patients complained about tremor in the hands. All patients had foot deformities, two patients had mild scoliosis. Two patients had sensorineural deafness. One patient with c.631T>C mutation had CNS involvement. Mean median motor velocity was 34.9± 5.2 (ranges 25–41) m/s in males, 36.7± 5.6 (ranges 32–43) m/s in females. Seventeen different mutations in GJB1 were indentified in our families and five of them were novel. Conclusions: Our data indicates the marked phenotypic variability in CMT-X as previously described in literature and we also described novel mutations in GJB1. Disclosure: Dr. Parman has nothing to disclose. Dr. Durmus has nothing to disclose. Dr. Candayan has nothing to disclose. Dr. Akcay has nothing to disclose. Dr. Yunisova has nothing to disclose. Dr. Ulukan has nothing to disclose. Dr. Serdaroglu has nothing to disclose. Dr. Deymeer has nothing to disclose. Dr. Battaloglu has nothing to disclose.