Genetic diagnosis in Lafora disease: genotype-phenotype correlations and diagnostic pitfalls.

Journal Article (Journal Article)

Lafora disease (LD) can be diagnosed by skin biopsy, but this approach has both false negatives and false positives. Biopsies of other organs can also be diagnostic but are more invasive. Genetic diagnosis is also possible but can be inconclusive, for example, in patients with only one heterozygous EPM2A mutation and patients with apparently homozygous EPM2B mutations where one parent is not a carrier of the mutation. We sought to identify occult mutations and clarify the genotypes and confirm the diagnosis of LD in patients with apparent nonrecessive disease inheritance. We used single nucleotide polymorphism, quantitative PCR, and fluorescent in situ hybridization analyses. We identified large EPM2A and EPM2B deletions undetectable by PCR in the heterozygous state and describe simple methods for their routine detection. We report a coding sequence change in several patients and describe why the pathogenic role of this change remains unclear. We confirm that adult-onset LD is due to EPM2B mutations. Finally, we report major intrafamilial heterogeneity in age at onset in LD.

Full Text

Duke Authors

Cited Authors

  • Lohi, H; Turnbull, J; Zhao, XC; Pullenayegum, S; Ianzano, L; Yahyaoui, M; Mikati, MA; Quinn, NP; Franceschetti, S; Zara, F; Minassian, BA

Published Date

  • March 27, 2007

Published In

Volume / Issue

  • 68 / 13

Start / End Page

  • 996 - 1001

PubMed ID

  • 17389303

Electronic International Standard Serial Number (EISSN)

  • 1526-632X

Digital Object Identifier (DOI)

  • 10.1212/01.wnl.0000258561.02248.2f


  • eng

Conference Location

  • United States