title: Novel mutation in the NHLRC1 gene in a Malian family with a severe phenotype of Lafora disease.
abstract: 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.
authors.affiliation: Department of Neurosciences, University of Bamako, Bamako, Mali.
authors.forename: M
authors.initials: M
authors.lastname: Traoré
authors.forename: G
authors.initials: G
authors.lastname: Landouré
authors.forename: W
authors.initials: W
authors.lastname: Motley
authors.forename: M
authors.initials: M
authors.lastname: Sangaré
authors.forename: K
authors.initials: K
authors.lastname: Meilleur
authors.forename: S
authors.initials: S
authors.lastname: Coulibaly
authors.forename: S
authors.initials: S
authors.lastname: Traoré
authors.forename: B
authors.initials: B
authors.lastname: Niaré
authors.forename: F
authors.initials: F
authors.lastname: Mochel
authors.forename: A
authors.initials: A
authors.lastname: La Pean
authors.forename: A
authors.initials: A
authors.lastname: Vortmeyer
authors.forename: H
authors.initials: H
authors.lastname: Mani
authors.forename: K H
authors.initials: KH
authors.lastname: Fischbeck