Further evidence of Fukutin mutations as a cause of childhood onset limb-girdle muscular dystrophy without mental retardation

Rebecca L Puckett; Steven A Moore; Thomas L Winder; Tobias Willer; Stephen G Romansky; Kelly King Covault; Kevin P Campbell; Jose E Abdenur

doi:10.1016/j.nmd.2009.03.001

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Further evidence of Fukutin mutations as a cause of childhood onset limb-girdle muscular dystrophy without mental retardation

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Further evidence of Fukutin mutations as a cause of childhood onset limb-girdle muscular dystrophy without mental retardation

Rebecca L Puckett, Steven A Moore, Thomas L Winder, Tobias Willer, Stephen G Romansky, Kelly King Covault, Kevin P Campbell and Jose E Abdenur

Neuromuscular disorders : NMD, Vol.19(5), pp.352-356

2009

DOI: 10.1016/j.nmd.2009.03.001

PMCID: PMC2698593

PMID: 19342235

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Abstract

The dystroglycanopathies comprise a clinically and genetically heterogeneous group of muscular dystrophies characterized by deficient glycosylation of α-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 α-dystroglycan glycoepitope immunostaining. Immunoblots revealed hypoglycosylation of α-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 α-dystroglycan hypoglycosylation in skeletal muscle.

Dystroglycanopathy

Fukuyama congenital muscular dystrophy (FCMD)

Fukutin (FKTN)

Limb-girdle muscular dystrophy (LGMD)

α-Dystroglycan

Details

Title: Subtitle: Further evidence of Fukutin mutations as a cause of childhood onset limb-girdle muscular dystrophy without mental retardation
Creators: Rebecca L Puckett - Children’s Hospital of Orange County, Division of Metabolic Disorders, 455 S Main St., Orange, CA 92868, USA
Steven A Moore - Department of Pathology, University of Iowa, Iowa City, USA
Thomas L Winder - Department of Pathology, University of Iowa, Iowa City, USA
Tobias Willer - Department of Molecular Physiology and Biophysics, Howard Hughes Medical Institute, University of Iowa, Iowa City, USA
Stephen G Romansky - Department of Pathology, Long Beach Memorial Medical Center, Long Beach, CA, USA
Kelly King Covault - Children’s Hospital of Orange County, Division of Metabolic Disorders, 455 S Main St., Orange, CA 92868, USA
Kevin P Campbell - Department of Molecular Physiology and Biophysics, Howard Hughes Medical Institute, University of Iowa, Iowa City, USA
Jose E Abdenur - Children’s Hospital of Orange County, Division of Metabolic Disorders, 455 S Main St., Orange, CA 92868, USA
Resource Type: Journal article
Publication Details: Neuromuscular disorders : NMD, Vol.19(5), pp.352-356
DOI: 10.1016/j.nmd.2009.03.001
PMID: 19342235
PMCID: PMC2698593
NLM abbreviation: Neuromuscul Disord
ISSN: 0960-8966
eISSN: 1873-2364
Publisher: Elsevier B.V
Language: English
Date published: 2009
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute
Record Identifier: 9984020737002771

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