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. 2009 Oct;10(4):319-23.
doi: 10.1007/s10048-009-0190-4. Epub 2009 Mar 26.

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

M Traoré  1 , G Landouré, W Motley, M Sangaré, K Meilleur, S Coulibaly, S Traoré, B Niaré, F Mochel, A La Pean, A Vortmeyer, H Mani, K H Fischbeck
Affiliations

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

M Traoré et al. Neurogenetics. 2009 Oct.

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.

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Figures

Fig. 1
Fig. 1
Pedigree of the family. Note the consanguinity in both families with at least one affected individual in each
Fig. 2
Fig. 2
Mutant malin fails to reduce the steady-state levels of laforin as efficiently as wild-type malin in Cos7 cells transfected with recombinant tagged proteins
See this image and copyright information in PMC

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