Document Detail

New FKRP mutations causing congenital muscular dystrophy associated with mental retardation and central nervous system abnormalities. Identification of a founder mutation in Tunisian families.
MedLine Citation:
PMID:  14652796     Owner:  NLM     Status:  MEDLINE    
The congenital muscular dystrophies (CMD) constitute a clinically and genetically heterogeneous group of autosomal recessive myopathies. Patients show congenital hypotonia, muscle weakness, and dystrophic changes on muscle biopsy. Mutations in four genes (FKT1, POMGnT1, POMT1, FKRP) encoding putative glycosyltransferases have been identified in a subset of patients characterized by a deficient glycosylation of alpha-dystroglycan on muscle biopsy. FKRP mutations account for a broad spectrum of patients with muscular dystrophy, from a severe congenital form with or without mental retardation (MDC1C) to a much milder limb-girdle muscular dystrophy (LGMD2I). We identified two novel homozygous missense FKRP mutations, one, A455D, in six unrelated Tunisian patients and the other, V405L, in an Algerian boy. The patients, between the ages of 3 and 12 years, presented with a severe form of MDC1C with calf hypertrophy and high serum creatine kinase levels. None had ever walked. Two had cardiac dysfunction and one strabismus. They all had mental retardation, microcephaly, cerebellar cysts, and hypoplasia of the vermis. White matter abnormalities were found in five, mostly when cranial magnetic resonance imaging was performed at a young age. These abnormalities were shown to regress in one patient, as has been observed in patients with Fukuyama CMD. Identification of a new microsatellite close to the FKRP gene allowed us to confirm the founder origin of the Tunisian mutation. These results strongly suggest that particular FKRP mutations in the homozygous state induce structural and clinical neurological lesions in addition to muscular dystrophy. They also relate MDC1C to other CMD with abnormal protein glycosylation and disordered brain function.
Nacim Louhichi; Chahnez Triki; Susana Quijano-Roy; Pascale Richard; Samira Makri; Mériem Méziou; Brigitte Estournet; Slah Mrad; Norma B Romero; Hammadi Ayadi; Pascale Guicheney; Faiza Fakhfakh
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-12-02
Journal Detail:
Title:  Neurogenetics     Volume:  5     ISSN:  1364-6745     ISO Abbreviation:  Neurogenetics     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-03-01     Completed Date:  2004-05-17     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  9709714     Medline TA:  Neurogenetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  27-34     Citation Subset:  IM    
Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Avenue Majida Boulila, 3029 Sfax, Tunisia.
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MeSH Terms
Abnormalities, Multiple / genetics*
Cerebellum / abnormalities*
Child, Preschool
Family Health
Founder Effect
Intellectual Disability / complications,  genetics*
Magnetic Resonance Imaging
Muscular Dystrophies / complications,  congenital,  genetics*
Proteins / genetics*,  metabolism
Reg. No./Substance:
0/FKRP protein, human; 0/Proteins

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