Search

Background: Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous disorder that can be an autosomal-dominant, autosomal-recessive, or X-linked disease. The most common autosomal-dominant form of the disease derives from mutations in the SPAST gene., Methods: The aim of this study was to analyze 49 patients diagnosed with HSP from the Estonian population for sequence variants of the SPAST gene and to describe the associated phenotypes. Healthy control individuals (n = 100) with no family history of HSP were also analyzed. All patient samples were screened using denaturing high performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA) assay. Samples with abnormal DHPLC and MLPA profiles were sequenced, with the same regions sequenced in control samples., Results: Sequence variants of SPAST were identified in 19/49 HSP patients (38.8%), twelve among them had pathogenic mutations. Within the latter group there was one sporadic case. Eight patients had pure, and four - complex HSP. The twelve variants were identified: seven pathogenic (c.1174-1G>C, c.1185delA, c.1276C>T, c.1352_1356delGAGAA, c.1378C>A, c.1518_1519insTC, c.1841_1842insA) and five non-pathogenic (c.131C>T, c.484G>A, c.685A>G, c.1245+202delG, c.1245+215G>C). Only 2 of these mutations had previously been described (c.131C>T, c.1245+202delG). Three mutations, c.1174-1G>C, c.1276 C>T, c.1378C>A, showed intrafamilial segregation., Conclusion: This study identified new variants of the SPAST gene which included benign missense variants and short insertions/deletions. No large rearrangements were found. Based on these data, 7 new pathogenic variants of HSP are associated with clinical phenotypes.

Epidemiological studies were performed in South Estonia to establish the prevalence rate of multiple sclerosis (MS) and motor neurone disease (MND). The case finding method included information from the hospital records of the central hospital in the region-the University Hospital (for MS from 1942 to 1989), from all neurologists in the region, from the Estonian MS Society and Association of Muscular Disorders, and from nursing homes in the region. The prevalence day was 31 December 1989. MND incidence was established for the period of 1986-1995. The results demonstrated high prevalence rates of MS among native Estonians (55.3 per 100 000), somewhat lower prevalence among native-born representatives of other nationalities (43.6 per 100 000) and the lowest prevalence rate of MS among non-Estonian immigrants (26.6 per 100 000). The differences were not statistically significant. The results for MND demonstrated the opposite pattern. The mean annual incidence rate of MND for 10 years was statistically significantly higher among people of other nationalities (2.5 per 100 000) and Russians (2.6 per 100 000), and lower in native-born Estonians (1.1 per 100 000). No differences in health care or clinical picture were established. The reasons for the demonstrated differences in MND incidence remain unclear., (Copyright 1999 Lippincott Williams & Wilkins.)