Immunohistochemical Study of Dystrophin Associated Glycoproteins in Limb-girdle Muscular Dystrophies

Transcription

1 Dystrophin Immunohistochemical Study of Dystrophin Associated Glycoproteins in Limb-girdle Muscular Dystrophies NSC B ( Peroxidase -AntiPeroxidase Immnofluorescence) Abstract (dystrophin) To differentiate autosomal recessive limb-girdle muscular dystrophies (LGMD) α-,β-,γ- sarcoglycan and congenital muscular dystrophies (CMD) we applied schematic merosin immunostaining on muscle biopsies of 24 LGMD patients and 4 CMD patients with dysferlin antibodies against -, - and - LBMD2B sarcoglycan. Immunostaining with merosin CK (>4000U/L) was also applied to patients with CMD. There was no reduced immunoreactivity in (Miyoshi myopathy) all the patients. Dysferlin immunostaining showed markedly reduced staining in 5 patients, thus leading to the diagnosis of LGMD2B. All these 5 patients had very high sarcoglycan 1

2 CK level (>4000U/L) and various degree of distal weakness (besides proximal weakness). One patient s older sister had the clinical presentation of Miyoshi myopathy. In conclusion, LGMD due to sarcoglycan deficiency was not detected in our cases but 5 patients with LGMD2B were identified. Keywords: Limb-girdle muscular dystrophy, congenital muscular dystrophy, dystrophin associated glycoprotein, merosin, sarcoglycan, dysferlin, immunohistochemistry biopsies have normal immunostaining of (Limb-girdle muscular dystrophin. dystrophy, LGMD) Immunostaing of -, - and sarcoglycan monoclonal antibodies (LGMD1) (Novocastra) were all positive. Merosin (LGMD2) LGMD2 (Chemicon) immunostaining were positive in LGMD2A-H patients with CMD. (Dystrophin) Five biopsies showed markedly decreased immunostaining of Type 2C 2D 2E 2F ( gift from Kevin P. Campbell). -, -, - sarcoglycan LGMD2A calpain3, LGMD2B dysferlin 1.In Taiwan, diagnoses of limb-girdle Laminin2 alpha-2 chain (merosin) Results: Totally 28 patients with autosomal recessive or sporadic LGMD were identified. Four biopsies with end- stage muscle were excluded for further immunostaining. Four patients with CMD were identified. All these Discussion: dysferlin dystrophy were often not specified. Differential diagnosis can be achieved by schematic immunostaining. 2

3 2.Recently -sarcoglycan deficiency were reported in two Taiwanese adults. In our series we did not find any adult onset LGMD with sarcoglycan deficiency. Sarcoglycan deficiency probably can only explain a small portion of adult LGMD patients but the majority are due to other types. 3.LGMD2B were identified in 5 of our patients, who all have very high CK levels (4910 to 30000U/L). In patients with very high CK level but with normal dystrophin, LGMD2B should be considered. 4. In patients with dysferlin deficiency, various degrees of distal weakness were observed. One patient showed marked posterior compartment weakness in legs. This patient could have been diagnosed as Miyoshi myopathy if examined in an earlier stage. Progression of Miyoshi myopathy can lead to significant proximal weakness and hence be diagnosed as limbgirdle muscular dystrophy. Careful examination of the distal parts may give us some hint. 5.Miyoshi myopathy and limb girdle muscular dystrophy can occur in the same family. Recent data indicate that there is phenotypic heterogeneity among different individuals with the same dysferlin gene mutation. Genetic study of Taiwanese family with MM may further delineate genotype-phenotype relationship. 2 sarcoglycan 3

4 - sarcoglycan deficiency muscular dystrophy in two adults. J Formos Med Assoc 2000;99:

5 5