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

H. Lohi, J. Turnbull, X. C. Zhao, S. Pullenayegum, L. Ianzano, M. Yahyaoui, M. A. Mikati, S. Franceschetti, F. Zara, B. A. Minassian

Research output: Contribution to journalReview articlepeer-review

32 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)996-1001
Number of pages6
JournalNeurology
Volume68
Issue number13
DOIs
StatePublished - Mar 2007

ASJC Scopus subject areas

  • Clinical Neurology

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