Duplication of dystrophin gene and dissimilar clinical phenotype in the same family.
We report here three related patients with a duplication of exons 19-41 of the dystrophin gene, having dissimilar clinical phenotype and dystrophin immunohistochemistry. Two brothers aged six and three years had myalgia, proximal muscular weakness and hypertrophic calves, with 10- 20-fold increase of serum creatine kinase. Muscle biopsy showed dystrophic changes and reduced, patchy binding of dystrophin. The clinical and laboratory findings were consistent with a diagnosis of Becker muscular dystrophy with early onset. Their 14-year-old cousin had only mild hyperCKemia. His muscle biopsy was normal with only mild reduction of dystrophin immunostaining. At follow-up, he is still without symptoms and signs at age 19. All three patients had the same gene duplication and an increased dystrophin size of 507 kDa. Expression of the dystrophin-associated glycoproteins adhalin, alpha-dystroglycan, and beta-dystroglycan were normal in the three patients. An intrafamilial variability in patients carrying a partial duplication of the dystrophin gene may be related to a quantitative difference in mRNA.
Toscano
A
A
Clinica Neurologica 2, University of Messina, Italy.
Vitiello
L
L
Comi
G P
GP
Galvagni
F
F
Miorin
M
M
Prelle
A
A
Fortunato
F
F
Bardoni
A
A
Mora
M
M
Fiumara
A
A
D015139:Blotting, Southern; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000096:biosynthesis; D016189:Dystrophin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D005810:Multigene Family / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype
D016189:Dystrophin; D004247:DNA