Novel mutation in the NHLRC1 gene in a Malian family with a severe phenotype of Lafora disease

We studied a Malian family with parental consanguinity and two of eight siblings affected with late-childhood-onset progressive myoclonus epilepsy and cognitive decline, consistent with the diagnosis of Lafora disease. Genetic analysis showed a novel homozygous single-nucleotide variant in the NHLRC...

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Bibliographic Details
Published in:Neurogenetics 2009-10, Vol.10 (4), p.319-323
Main Authors: Traoré, M., Landouré, G., Motley, W., Sangaré, M., Meilleur, K., Coulibaly, S., Traoré, S., Niaré, B., Mochel, F., La Pean, A., Vortmeyer, A., Mani, H., Fischbeck, K. H.
Format: Article
Language:English
Subjects:
Adolescent
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Brain - pathology
Carrier Proteins - genetics
Child
Consanguinity
DNA Mutational Analysis
Female
Fundamental and applied biological sciences. Psychology
Genetic disorders
Genetics of eukaryotes. Biological and molecular evolution
Genotype & phenotype
Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy
Human Genetics
Humans
Lafora Disease - genetics
Lafora Disease - pathology
Lafora Disease - physiopathology
Male
Mali
Medical sciences
Minority & ethnic groups
Molecular and cellular biology
Molecular Medicine
Mutation
Mutation, Missense
Nervous system (semeiology, syndromes)
Neurological disorders
Neurology
Neurosciences
Original
Original Article
Pedigree
Polymorphism, Single Nucleotide
Population genetics
Ubiquitin-Protein Ligases
Vertebrates: nervous system and sense organs
Young Adult
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Summary:We studied a Malian family with parental consanguinity and two of eight siblings affected with late-childhood-onset progressive myoclonus epilepsy and cognitive decline, consistent with the diagnosis of Lafora disease. Genetic analysis showed a novel homozygous single-nucleotide variant in the NHLRC1 gene, c.560A>C, producing the missense change H187P. The changed amino acid is highly conserved, and the mutation impairs malin's ability to degrade laforin in vitro. Pathological evaluation showed manifestations of Lafora disease in the entire brain, with particularly severe involvement of the pallidum, thalamus, and cerebellum. Our findings document Lafora disease with severe manifestations in the West African population.
ISSN:1364-6745
1364-6753
DOI:10.1007/s10048-009-0190-4