Clinical correlations in 16 patients with total or partial laminin alpha 2deficiency characterized using antibodies against 2 fragments of the protein

Background: Many patients with classic congenital muscular dystrophy have b een found to have partial or total deficiency of the alpha 2 chain of lamin in 2 (merosin). This deficiency has mostly been studied using only 1 antibo dy against a fragment of the protein. Objectives: To characterize the expression of laminin alpha 2 in the skelet al muscle of patients with laminin alpha 2 deficiency using antibodies agai nst 2 different portions of the protein and to correlate the immunochemical findings with clinical phenotype. Methods: We studied 4 patients with to tal lack of laminin alpha 2 and 12 w ith partial laminin alpha 2 deficiency with immunohistochemical techniques and Western blot analysis. We used antibodies recognizing an 80-kd fragment toward the C-terminus and a 300-kd fragment toward the amino-terminal. Pat ient characteristics examined were functional compromise, magnetic resonanc e imaging or computed tomography of the brain, electromyography, evoked pot entials, and creatine kinase levels. Results: In 4 patients, immunohistochemical analysis revealed no reactivity to either antibody; in 2 patients, the 300-kd fragment alone was partially expressed; in 2 patients, the 80-kd fragment alone was partially expressed ; and in 8 patients, both fragments were partially expressed. Immunoblot an alysis revealed bands of reduced intensity and normal molecular weight gene rally corresponding to the immunohistochemical findings. Absence of both fr agments or of one with reduction of the other always produced a severe clin ical phenotype, while a milder clinical phenotype was observed when bo th f ragments were partially expressed. Conclusions: Extent of laminin alpha 2 deficiency in most cases correlates with clinical phenotype but not with peripheral and central white matter ab normalities. Skin biopsy specimens may reveal laminin alpha 2 deficiency in patients who have normal laminin alpha 2 levels in muscle biopsy specimens .