Becker 근육병증 환아 두명에서 확인한 새로운 DMD 유전자 변이
Identification of Two novel DMD mutations in patients with Becker muscular dystrophy
Abstract
Introduction: Duchenne and Becker muscular dystrophies are X-linked neuromuscular disorders characterized by progressive muscle weakness and severe skeletal muscle degeneration. Becker muscular dystrophy is a milder form with a later onset and a much longer survival. The differential diagnosis of BMD and DMD are often dependent on the mutation identified in the DMD gene in affected patients. However, when a novel DMD mutation is identified, the differential diagnosis should be based on the muscle biopsy findings with other clinical findings. Here we describe two Korean patients with Becker muscular dystrophy confirmed by muscle biopsy and genetic testing. Methods: The clinical findings of two BMD patients were reviewed. MLPA was done for genetic diagnosis, and muscle biopsy was undergone for checking histopathology. Results: Two patients shared the common clinical features of patients with BMD, but with different severity. Patient 1 had mild muscle weakness, Gower sign, and calf muscle pseudohypertrophy, and patient 2 only had mild calf muscle enlargement and had been nearly asymptomatic. CK levels were elevated to similar degree in both of them, and cardiac function was normal. The results of muscle biopsies were different between them, patient 1 had a few degeneration changes and patient 2 had a normal histopathologic feature. Two different novel exonic deletions of the DMD gene were identified; exon 78 and 79 deletions of the DMD gene in patient 1 and exon 30-38 deletions in patient 2. The expression of dystrophin was abundant in the muscle tissues of patient 2 with exon 30-38 deletions in contrast to a patchy intermittent expression in the patient 1 with exon 78-79 deletion. Conclusion: It is expected that exon 30-38 deleted dystrophin is more structurally stable than the dystrophin with exon 78-79 deletion, and is associated with milder BMD phenotype. Current study suggests a wide range of severity among BMD patients with different clinical and histological characteristics.