title: Further evidence of Fukutin mutations as a cause of childhood onset limb-girdle muscular dystrophy without mental retardation.
abstract: The dystroglycanopathies comprise a clinically and genetically heterogeneous group of muscular dystrophies characterized by deficient glycosylation of alpha-dystroglycan. Mutations in the fukutin (FKTN) gene have primarily been identified among patients with classic Fukuyama congenital muscular dystrophy (FCMD), a severe form of dystroglycanopathy characterized by CMD, cobblestone lissencephaly and ocular defects. We describe two brothers of Caucasian and Japanese ancestry with normal intelligence and limb-girdle muscular dystrophy (LGMD) due to compound heterozygous FKTN mutations. Muscle biopsy showed a dystrophy with selectively reduced alpha-dystroglycan glycoepitope immunostaining. Immunoblots revealed hypoglycosylation of alpha-dystroglycan and loss of laminin binding. FKTN gene sequencing identified two variants: c.340G>A and c.527T>C, predicting missense mutations p.A114T and p.F176S, respectively. Our results provide further evidence for ethnic and allelic heterogeneity and the presence of milder phenotypes in FKTN-dystroglycanopathy despite a substantial degree of alpha-dystroglycan hypoglycosylation in skeletal muscle.
authors.affiliation: Children's Hospital of Orange County, Division of Metabolic Disorders, Orange, CA 92868, USA. rpuckett@choc.org
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Puckett
authors.forename: Steven A
authors.initials: SA
authors.lastname: Moore
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Winder
authors.forename: Tobias
authors.initials: T
authors.lastname: Willer
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Romansky
authors.forename: Kelly King
authors.initials: KK
authors.lastname: Covault
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Campbell
authors.forename: Jose E
authors.initials: JE
authors.lastname: Abdenur