Mutations in the FKRP gene can cause muscle-eye-brain disease and Walker–Warburg syndrome

• Published in: Journal of medical genetics Vol. 41; no. 5; p. e61
• Main Authors: Beltran-Valero de Bernabé, D, Voit, T, Longman, C, Steinbrecher, A, Straub, V, Yuva, Y, Herrmann, R, Sperner, J, Korenke, C, Diesen, C, Dobyns, W B, Brunner, H G, van Bokhoven, H, Brockington, M, Muntoni, F
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01-05-2004; BMJ Publishing Group LTD; BMJ Group
• Subjects: Age; Brain - abnormalities; Brain - pathology; Brain diseases; Child; congenital muscular dystrophy; Cysts; Defects; Electronic Letter; Eye Abnormalities - genetics; Female; FKRP; Genetic Predisposition to Disease; Genotype & phenotype; Humans; Infant, Newborn; Intellectual disabilities; Kinases; Magnetic Resonance Imaging; Male; Muscle, Skeletal; muscle-eye-brain disease; Muscular Dystrophies - diagnosis; Muscular Dystrophies - genetics; Muscular dystrophy; Musculoskeletal system; Mutation; Mutation, Missense; Patients; Proteins; Proteins - genetics; Syndrome; Walker–Warburg syndrome; α-dystroglycan glycosylation
• DOI: 10.1136/jmg.2003.013870
• EISSN: 1468-6244
• ISSN: 0022-2593; 1468-6244

12 Clinical features of MDC1C are onset in the first weeks of life, inability to walk, muscle hypertrophy, and highly elevated serum creatine kinase (CK) levels. 12, 13 Mutations in the same gene also underlie a milder form of muscular dystrophy (limb girdle muscular dystrophy 2I or LGMD2I), characterised by childhood or adult onset and a relatively benign course, although dilated cardiomyopathy is a common feature [OMIM 607115]. 24, 25 Normal dystroglycan expression and the proper glycosylation of its α subunit are required for binding to a number of extracellular ligands, including laminin, neurexin, and agrin. 6, 7, 18, 23 Disruption of these interactions results in defects of basement membranes in both skeletal muscle and brain. 6, 7 The integrity of the pial basement membrane, which covers the surface of the brain, is necessary for the organisation of a subpopulation of glial cells, the radial glial cells, which guide the migration of neurones on their inside out journey from the proliferative periventricular regions to the surface of the brain. 7, 26, 27 Defects in the pial basement membrane result in the migration of neurones and glial cells beyond the interrupted pial membrane, giving rise to the cobblestone appearance of the brain. 18, 28, 29 Cobblestone lissencephaly is a consistent feature of FCMD, MEB, WWS, the Largemyd mouse, and MDC1D, but has never been previously described in patients with MDC1C or LGMD2I.