Genetic Landscape of Dystrofin Gene Deletions and Duplications From Turkey: A Single Center Experience

Abstract

Objective: Dystrophinopathies are the most frequently researched neuromuscular disease group due to their characteristic and diverse clinical and genetic spectrum. This study aims to evaluate the deletion and duplication profile of the dystrophin gene in Turkey by investigating data from a tertiary center.Material and Methods: Dystrophin MLPA and microarray results of 53 patients, 49 with a dystrophinopathy and 4 with a neurogenetic and syndromic disorder pre-diagnosis, who were referred to the Medical Genetics Clinic of Ankara City Hospital between February 2019-December 2020 were retrospectively evaluated.Results: Of the 53 patients, 4 had various exon duplications and 49 had deletions. 33 of these mutations caused frame-shift (62.3%), while 20 caused in-frame (37.7%) changes. Fifty (94.3%) patients underwent maternal studies and 14 (26.4%) of these had de novo mutations. Mutations were observed most frequently in the central rod domain (69.7%) followed by the actin-binding domain (7.5%) of the dystrophin gene and 12 of 33 patients with frameshift mutation (36%) patients were found to be candidates for the exon skipping treatments that are still subject to clinical research. Conclusion:This study has shed light on the incidence of dystrophin deletion/duplication mutations in our population and has revealed that a majority of patients are suitable candidates for treatments which are still not in routine use. Considering ever-growing number of dystrophin gene-based treatment options, data on population-specific mutation types is of great importance.