Clinical, Immunohistochemical, and Genetic Analysis in Dystrophinopathy

J Korean Neurol Assoc > Volume 22(5); 2004 > Article

Journal of the Korean Neurological Association 2004;22(5): 508-515.

Dystrophinopathy 환자의 임상적, 면역조직화학적 및 유전학적 분석

나상준, 강성웅* 김원주 김태승† 최영철

연세대학교 의과대학 신경과학교실, 재활의학과학교실*, 병리학교실†

Clinical, Immunohistochemical, and Genetic Analysis in Dystrophinopathy

Sang-Jun Na

Departments of Neurology, Rehabilitation Medicine*, Pathology†, Yonsei University College of Medicine, Seoul, Korea

Abstract

Background: Dystrophin deficient muscular dystrophies (dystrophinopathies) are the most common form of muscular dystrophy with variable clinical phenotypes from the severe Duchenne to the milder Becker forms (DMD/BMD). Dystrophinopathies are X-linked recessive diseases caused by the mutation of the dystrophin gene. Western blot and immunohistochemical staining for dystrophin, and exon deletion analysis by multiplex polymerase chain reaction (PCR) are important diagnostic tools. We investigated the relationship between the clinical characteristics, immunohistochemistry for dystrophin, and the pattern of exon deletions in patients with dystrophinopathy.
Methods: We reviewed the clinical and laboratory findings of 35 male patients diagnosed as DMD/BMD. Genomic DNA of the 35 patient was analyzed by multiplex PCR using 19 primer sets of dystrophin gene. Immunohistochemistry for dystrophin of muscle biopsy tissue was performed in all cases.
Results: The mean age of symptom onset in 35 patients was 4.6±2.7 years [range, 2-15 years]. Twenty-four of 35 (68.6%) patients showed complete loss (C-, Rod-, N terminal), and 11 of 35 (31.4%) patient showed incomplete loss of dystrophin in immunohistochemistry. Of the 35 patients, 20 had deletions (57%) by multiplex PCR analysis. Sixteen of 20 patients (80%) had exon deletions between exon 45 and 52.
Conclusions: Immunohistochemistry of biopsied muscle specimen is an important diagnostic method for expression and localization of dystrophin. The exon deletion analysis by multiplex PCR using peripheral blood is also a simple and useful test for the diagnosis of dystrophinopathies, although it has limited sensitivity.Key Words: Dystrophin, Muscular Dystrophies, Immunohistochemistry