A novel FKRP mutation in congenital muscular dystrophy disrupts the dystrophin glycoprotein complex.
Mutations in the gene encoding fukutin related protein (FKRP) produce a spectrum of disease including congenital muscular dystrophy and limb girdle muscular dystrophy. FKRP is one member of a class of molecules thought to be glycosyltransferases that mediate O-linked glycosylation. The primary target of these glycosyltransferases is thought to be dystroglycan. We now report two unrelated Mexican children with congenital muscular dystrophy who each have the identical, novel 1387A>G, N463D mutation. Muscle biopsies from these children show a reduction of alpha-dystroglycan and also show reduction of beta-dystroglycan, and alpha-, beta-, and gamma-sarcoglycan, suggesting that FKRP mutations can perturb membrane associated proteins beyond dystroglycan.
MacLeod
Heather
H
Department of Medicine, Section of Cardiology, The University of Chicago, Chicago, IL 60637, USA.
Pytel
Peter
P
Wollmann
Robert
R
Chelmicka-Schorr
Ewa
E
Silver
Kenneth
K
Anderson
Rebecca Brown
RB
Waggoner
Darrel
D
McNally
Elizabeth M
EM
D001216:Asparagine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D002675:Child, Preschool; D016189:Dystrophin / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D010430:Pentosyltransferases; D011506:Proteins / Q000235:genetics*
D016189:Dystrophin; D006023:Glycoproteins; D011506:Proteins; D001224:Aspartic Acid; D001216:Asparagine; C443107:FKRP protein, human; D010430:Pentosyltransferases