title: Clinical and genetic data on Lafora disease patients of Serbian/Montenegrin origin.
abstract: Lafora disease (LD) is an autosomal recessive, progressive disorder characterized by myoclonus and seizures, inexorable neurologic deterioration, cognitive decline and poor prognosis. LD is caused by mutations either in the EPM2A or in NHLRC1 genes. Here we report clinical and genetic findings on 14 LD patients from 10 families of Serbian/Montenegrin origin. Molecular diagnostics was performed by sequencing the coding regions of the EPM2A and NHLRC1 genes. In addition, haplotype analysis of the chromosomes carrying the two most frequent mutations (c.1048-1049delGA and deletion of the whole NHLRC1 gene) using eight different markers flanking the NHLRC1 gene was conducted. We identified one new mutation (c.1028T>C) along with the 3 previously reported mutations (c.1048-1049delGA, c.990delG, deletion of the whole NHLRC1 gene), all of which were located on the NHLRC1 gene. The two predominant mutations (c.1048-1049delGA and complete NHLRC1 gene deletion) appear to be founder mutations. In addition to documenting the genetic heterogeneity observed for LD, our study suggests that mutations in the NHLRC1 gene may be a common cause of LD in the Serbian/Montenegrin population, primarily because of a founder effect.
authors: Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Belgrade, Serbia.
authors: M
authors: M
authors: Kecmanović
authors: Clinic of Neurology and Psychiatry for Children and Youth, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors: N
authors: N
authors: Jović
authors: Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Belgrade, Serbia.
authors: M
authors: M
authors: Keckarević-Marković
authors: Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Belgrade, Serbia.
authors: D
authors: D
authors: Keckarević
authors: Clinic of Neurology and Psychiatry for Children and Youth, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors: G
authors: G
authors: Stevanović
authors: Clinic of Neurology and Psychiatry for Children and Youth, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors: P
authors: P
authors: Ignjatović
authors: Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Belgrade, Serbia.
authors: S
authors: S
authors: Romac
mesh_terms: D000293:Adolescent; D000483:Alleles; D001706:Biopsy; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D020192:Lafora Disease / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D009154:Mutation; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics; D012867:Skin / Q000378:metabolism / Q000473:pathology; D044767:Ubiquitin-Protein Ligases
chemical_list: D002352:Carrier Proteins; C478960:NHLRC1 protein, human; D044767:Ubiquitin-Protein Ligases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C114990:EPM2A protein, human
keywords: Lafora disease; NHLRC1 gene; Serbian/Montenegrin population; founder effect