title: A novel FKRP mutation in congenital muscular dystrophy disrupts the dystrophin glycoprotein complex.
abstract: 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.
authors.affiliation: Department of Medicine, Section of Cardiology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: MacLeod
authors.forename: Peter
authors.initials: P
authors.lastname: Pytel
authors.forename: Robert
authors.initials: R
authors.lastname: Wollmann
authors.forename: Ewa
authors.initials: E
authors.lastname: Chelmicka-Schorr
authors.forename: Kenneth
authors.initials: K
authors.lastname: Silver
authors.forename: Rebecca Brown
authors.initials: RB
authors.lastname: Anderson
authors.forename: Darrel
authors.initials: D
authors.lastname: Waggoner
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: McNally
mesh_terms: 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*
chemical_list: D016189:Dystrophin; D006023:Glycoproteins; D011506:Proteins; D001224:Aspartic Acid; D001216:Asparagine; C443107:FKRP protein, human; D010430:Pentosyltransferases