Mutations in the NHLRC1 gene are the common cause for Lafora disease in the Japanese population.

Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, India.
Journal of Human Genetics (Impact Factor: 2.53). 02/2005; 50(7):347-52. DOI: 10.1007/s10038-005-0263-7
Source: PubMed

ABSTRACT Lafora disease (LD) is a rare autosomal recessive genetic disorder characterized by epilepsy, myoclonus, and progressive neurological deterioration. LD is caused by mutations in the EMP2A gene encoding a protein phosphatase. A second gene for LD, termed NHLRC1 and encoding a putative E3 ubiquitin ligase, was recently identified on chromosome 6p22. The LD is relatively common in southern Europe, the Middle East, and Southeast Asia. A few sporadic cases with typical LD phenotype have been reported from Japan; however, our earlier study failed to find EPM2A mutations in four Japanese families with LD. We recruited four new families from Japan and searched for mutations in EPM2A . All eight families were also screened for NHLRC1 mutations. We found five independent families having novel mutations in NHLRC1. Identified mutations include five missense mutations (p.I153M, p.C160R, p.W219R, p.D245N, and p.R253K) and a deletion mutation (c.897insA; p.S299fs13). We also found a family with a ten base pair deletion (c.822-832del10) in the coding region of EPM2A. In two families, no EPM2A or NHLRC1 mutation was found. Our study, in addition to documenting the genetic and molecular heterogeneity observed for LD, suggests that mutations in the NHLRC1 gene may be a common cause of LD in the Japanese population.

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Available from: Shinichi Hirose, Jul 11, 2015
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    • "Two peaks are the result of a duplex PCR. PCR of 156 bp represents the control PCR used for normalization and the other is region of the NHLRC1 gene amplified with LD2L4R4 primers [9]. Below the peak, the first number is the length of PCR product in base pairs (bp), and the second is the area of the peaks. "
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