Article

Founder effect with variable age at onset in Arab families with Lafora disease and EPM2A mutation.

Neurology Service, Fundación Jiménez Díaz, Madrid, Spain.
Epilepsia (impact factor: 3.96). 06/2007; 48(5):1011-4. DOI:10.1111/j.1528-1167.2007.01004.x pp.1011-4
Source: PubMed

ABSTRACT We observed three apparently unrelated and geographically separate Arab families with Lafora disease in Israel and the Palestinian territories.
We clinically evaluated the families and analyzed their DNA for EPM2A mutations.
Of seven individuals with Lafora disease, the clinical onset varied from 13 to 20 years. All three families shared the same novel homozygous deletion in EPM2A. Haplotype analysis around the deletion showed that the families shared a common homozygous haplotype. The boundaries of this haplotype varied between families and even within one family.
We conclude that considerable variability in the age at onset of Lafora disease can occur within families. Identical mutations can be associated with the classic adolescent presentation, as well as late-onset cases. Haplotype analysis suggests that this EPM2A mutation arose many generations previously, so it may be of importance for cases distributed more widely in the Middle East.

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    Article: Lafora progressive myoclonus epilepsy: recent insights into cell degeneration.
    Carlos Spuch, Saida Ortolano, Carmen Navarro
    [show abstract] [hide abstract]
    ABSTRACT: Lafora disease (LD) is a fatal autosomal recessive form of progressive myoclonus epilepsy. Patients manifest myoclonus and tonic-clonic seizures, visual hallucinations, intellectual, and progressive neurologic deterioration beginning in adolescence. The two genes known to be involved in Lafora disease are EPM2A and NHLRC1 (EPM2B). The EPM2A gene encodes laforin, a dual-specificity protein phosphatase, and the NHLRC1 gene encodes malin, an E3-ubiquitin ligase. The two proteins interact with each other and, as a complex, are thought to regulate glycogen synthesis. It may also be considered as a disorder of carbohydrate metabolism because of the formation of polyglucosan inclusion bodies in neural and other tissues due to abnormalities of the proteins laforin or malin. The review also outlines important patents related to Lafora disease.
    Recent Patents on Endocrine Metabolic & Immune Drug Discovery 02/2012; 6(2):99-107.
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Keywords

classic adolescent presentation
 
clinical onset varied
 
common homozygous haplotype
 
EPM2A
 
EPM2A mutation
 
EPM2A mutations
 
families
 
geographically separate Arab families
 
haplotype varied
 
Identical mutations
 
Lafora disease
 
late-onset cases
 
Middle East
 
novel homozygous deletion
 
Palestinian territories
 
three families