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New FKRP mutations causing congenital muscular dystrophy associated with mental retardation and central nervous system abnormalities. Identification of a founder mutation in Tunisian families
- Source :
- neurogenetics, neurogenetics, 2004, 5 (1), pp.27-34. ⟨10.1007/s10048-003-0165-9⟩, neurogenetics, Springer Verlag, 2004, 5 (1), pp.27-34. ⟨10.1007/s10048-003-0165-9⟩
- Publication Year :
- 2004
- Publisher :
- HAL CCSD, 2004.
-
Abstract
- International audience; 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.
- Subjects :
- Male
Microcephaly
Glycosylation
[SDV.GEN] Life Sciences [q-bio]/Genetics
MESH: Founder Effect
Muscular Dystrophies
MESH: Magnetic Resonance Imaging
0302 clinical medicine
cerebellar cysts
Cerebellum
MESH: Mental Retardation
MESH: Child
Missense mutation
MESH: Proteins
Muscular dystrophy
Child
Genetics (clinical)
founder-haplotype
0303 health sciences
Fukutin-related protein
medicine.diagnostic_test
biology
Homozygote
MESH: Glycosylation
Magnetic Resonance Imaging
Founder Effect
Pedigree
3. Good health
Child, Preschool
Congenital muscular dystrophy
Female
medicine.symptom
MESH: Tunisia
FKRP gene
MESH: Homozygote
medicine.medical_specialty
Tunisia
MESH: Abnormalities, Multiple
MESH: Pedigree
mental retardation
Article
03 medical and health sciences
Cellular and Molecular Neuroscience
Intellectual Disability
Internal medicine
Fukuyama congenital muscular dystrophy
Genetics
medicine
Humans
Abnormalities, Multiple
Pentosyltransferases
030304 developmental biology
Family Health
[SDV.GEN]Life Sciences [q-bio]/Genetics
Muscle biopsy
MESH: Humans
business.industry
MESH: Child, Preschool
Proteins
Muscle weakness
MESH: Haplotypes
medicine.disease
MESH: Muscular Dystrophies
MESH: Cerebellum
MESH: Male
Endocrinology
Haplotypes
biology.protein
MESH: Family Health
business
MESH: Female
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 13646745 and 13646753
- Database :
- OpenAIRE
- Journal :
- neurogenetics, neurogenetics, 2004, 5 (1), pp.27-34. ⟨10.1007/s10048-003-0165-9⟩, neurogenetics, Springer Verlag, 2004, 5 (1), pp.27-34. ⟨10.1007/s10048-003-0165-9⟩
- Accession number :
- edsair.doi.dedup.....8247acf414900ee924fdcfe8c5697d53