Homozygous alpha-sarcoglycan mutation in two siblings: one asymptomatic and one steroid-responsive mild limb-girdle muscular dystrophy patient.
We describe a couple of siblings who have a homozygous mutation in the alpha-sarcoglycan gene and present a striking clinical difference in their phenotype; the brother is asymptomatic, and the sister is affected with mild limb-girdle muscular dystrophy. Drug therapy with a new steroid (deflazacort) was done over 6 months in the mild limb-girdle patient, and we observed objective benefit in muscle strength and in functional tests. Side effects were minimal. Immunohistochemistry for alpha-sarcoglycan showed reduced intensity of reaction in the limb-girdle dystrophy patient and was similar to normal in the asymptomatic case. A reduced amount of residual alpha-sarcoglycan protein level was found in their muscle biopsies. Unknown epigenetic or environmental factors may have an important role in determining protein and clinical phenotype expression. This is the first report of a patient with homozygous sarcoglycan gene mutation without overt muscle weakness in his adulthood. The spectrum of clinical phenotypes in sarcoglycanopathies is therefore wider than previously thought.
Angelini
C
C
Department of Neurology, Neuromuscular Center, University of Padua, Italy.
Fanin
M
M
Menegazzo
E
E
Freda
M P
MP
Duggan
D J
DJ
Hoffman
E P
EP
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D015153:Blotting, Western; D003402:Creatine Kinase / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D049030:Dystroglycans; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000737:chemistry / Q000473:pathology; D009136:Muscular Dystrophies / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011282:Pregnenediones / Q000627:therapeutic use; D049031:Sarcoglycans; D014057:Tomography, X-Ray Computed; D014158:Transcription, Genetic
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D008562:Membrane Glycoproteins; D011282:Pregnenediones; D049031:Sarcoglycans; D049030:Dystroglycans; D003402:Creatine Kinase; C021988:deflazacort