Genotype-Phenotype Evaluation In 476 Turkish Dystrophinopathy Patients (P5.089)

Abstract

OBJECTIVE: In this study, we aimed to evaluate genotype-phenotype correlation in a large Turkish cohort. BACKGROUND: Duchenne muscular dystrophy (DMD) and its less severe allelic form, Becker muscular dystrophy (BMD), are common X-linked recessive dystrophies caused by mutations in the dystrophin gene. Studies on the genotype-phenotype correlations on DMD/BMD in Turkey are limited. Identification of the characteristics of genotype and phenotype correlation may facilitate prognosis regarding clinical severity. Furthermore, several ongoing and planned clinical trials which aim at targeting specific DMD mutations highlight the importance of recognition of the genetic features in dystrophinopathy patients. DESIGN/METHODS: Clinical and genetic findings of 476 patients diagnosed with dystrophinopathy at the Department of Neurology, Istanbul Faculty of Medicine between 1993 and 2013 were retrospectively evaluated. Multiplex DNA amplifications of the dystrophin gene were carried out according to Chamberlain et al and Beggs et al. RESULTS: Two hundred eighty-nine patients were diagnosed with DMD and 187 with BMD. Deletions in the dystrophin gene represented 66.5 % of the mutations in DMD/BMD patients. Intron 44 was the most common starting breakpoint in Turkish DMD/BMD patients. In 76 % of the cases the deletions were detected in the region from exon 45 to exon 52 located in the central part of the gene. The most frequent deletions in DMD were deletions of exons 45-50 (8.6%), exon 45 (7%) and exon 44 (6.4%). Deletions in BMD were less heterogeneous, and the most frequent deletions were exons 45-47 (29.6%), exons 45-48 (21.3%) and exons 45-52 (7.4%). 76% of patients with deletions in dystrophin gene was consistent with the reading-frame hypothesis. The major exception was the deletions starting at exon 47. CONCLUSIONS: The majority of the deletions in our population are clustered in the two known hot-spot regions, and in 76% of cases deletions were detected in the region from exons 45 to 52. Our findings are comparable to those reported in other populations.

Disclosure: Dr. Durmus has nothing to disclose. Dr. Erginel-Unaltuna has nothing to disclose. Dr. Uyan has nothing to disclose. Dr. Çakar has nothing to disclose. Dr. Altinkaya has nothing to disclose. Dr. Guclu-Geyik has nothing to disclose. Dr. Deymeer has nothing to disclose. Dr. Parman has nothing to disclose. Dr. Tolun has nothing to disclose. Dr. Serdaroglu has nothing to disclose.