title: Mutations in the NHLRC1 gene are the common cause for Lafora disease in the Japanese population.
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.
authors: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, India.
authors: Shweta
authors: S
authors: Singh
authors: Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1, Hirosawa, Wako, Saitama 351-0198, Japan.
authors: Toshimitsu
authors: T
authors: Suzuki
authors: Tokyo Metropolitan Medical Center for Severely Handicapped, Tokyo, Japan.
authors: Akira
authors: A
authors: Uchiyama
authors: Tokyo Metropolitan Medical Center for Severely Handicapped, Tokyo, Japan.
authors: Satoko
authors: S
authors: Kumada
authors: National Rehabilitation Center for Disabled Children, Tokyo, Japan.
authors: Nobuko
authors: N
authors: Moriyama
authors: Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan.
authors: Shinichi
authors: S
authors: Hirose
authors: National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorder, Shizuoka, Japan.
authors: Yukitoshi
authors: Y
authors: Takahashi
authors: Department of Pediatric Neurology, Hamamatsu City Medical Center for Developmental Medicine, Shizuoka, Japan.
authors: Hideo
authors: H
authors: Sugie
authors: National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorder, Shizuoka, Japan.
authors: Koichi
authors: K
authors: Mizoguchi
authors: National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorder, Shizuoka, Japan.
authors: Yushi
authors: Y
authors: Inoue
authors: Segawa Neurological Clinic for Children, Tokyo, Japan.
authors: Kazue
authors: K
authors: Kimura
authors: Department of Reproductive and Developmental Medicine, Division of Pediatrics, Akita University School of Medicine, Akita, Japan.
authors: Yukio
authors: Y
authors: Sawaishi
authors: Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1, Hirosawa, Wako, Saitama 351-0198, Japan. yamakawa@brain.riken.jp.
authors: Kazuhiro
authors: K
authors: Yamakawa
authors: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, India.
authors: Subramaniam
authors: S
authors: Ganesh
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D017931:DNA Primers; D040461:Gene Components; D005820:Genetic Testing; D006801:Humans; D007564:Japan / Q000453:epidemiology; D020192:Lafora Disease / Q000453:epidemiology* / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D017422:Sequence Analysis, DNA; D044767:Ubiquitin-Protein Ligases
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; C478960:NHLRC1 protein, human; D044767:Ubiquitin-Protein Ligases; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C114990:EPM2A protein, human