Clinical and genetic data on Lafora disease patients of Serbian/Montenegrin origin.

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.

HD phenocopies--possible role of Saitohin gene.

Saitohin (STH) is located in the intron of the human gene for microtubule-associated protein tau. Q7R polymorphism has been identified in the STH gene. Some neurodegenerative disorders were found to be associated with the presence of certain STH allele. This study genotyped 37 subjects with diagnosis of Huntington's disease, but lacking mutations in HD, PRNP, JPH-3, and FTL genes for STH polymorphism. It was determined that Q allele of STH gene was over-represented in a tested group of patients (P > Pt). Over-representation of Q allele in a group of patients might be considered as genetic risk factor for HD like diseases.

MECP2 mutations in Serbian Rett syndrome patients.

BACKGROUND: Rett syndrome is a severe neurodevelopmental X-linked dominant disorder affecting 1/15,000 girls worldwide. Eight years ago, the MECP2 gene was associated with the devastating clinical features observed in Rett syndrome patients. OBJECTIVES: To investigate the spectrum and the frequency of MECP2 mutations in Serbian Rett syndrome patients. PATIENTS AND METHODS: We screened the MECP2 coding region by conventional mutational screening (single-strand conformation polymorphism/sequencing) in 24 patients of Serbian origin and in their 41 unaffected family members. In search for gene dosage alterations in seemingly mutation-negative girls, we developed a new, specific quantitative PCR method. RESULTS: Nineteen patients (79%) carried MECP2 mutations, five of which were novel (one nonsense mutation, one duplication and three deletions). Fourteen previously described disease-causing sequence changes and one polymorphism were also detected. Detailed case reports are given for the carriers of the novel mutations. Large MECP2 rearrangements cause Rett syndrome in a significant number of girls without 'classic' mutations in this gene. Therefore, we developed a specific quantitative PCR method, covering MECP2 exons 3 and 4, which previously has not been used for screening. No dosage alterations of the two exons were found in the four tested mutation-negative girls. CONCLUSIONS: This is the first genetic study of Rett syndrome in Serbian patients describing the MECP2 mutational and phenotypic spectrum in this population. Detailed clinical descriptions of this ethnically homogeneous patient population add to our knowledge of genotype/phenotype correlations in this severe condition.