Clinical, Immunohistochemical, and Genetic Analysis in Dystrophinopathy

Na, Sang Jun; Kang, Seong Woong; Kim, Won Joo; Kim, Tai Seung; Choi, Young Chul

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.