Screening for premutation in the FMR1 gene in male patients suspected of spinocerebellar ataxia.

Background And Purpose: The aim of this study was to determine the molecular basis of the disorder in patients suspected of spinocerebellar ataxias (SCAs) and search for premutation in the FMR1 gene causing FXTAS among patients in whom 9 SCA types were previously excluded.

Material And Methods: DNA obtained from 1385 patients suspected of SCA and 516 controls were used for molecular tests. DNA analysis was carried out by PCR reaction with specific primers. PCR products were separated in denaturing polyacrylamide gels in an ABIPrism 377 sequencer. Amplification of polymorphic regions embracing trinucleotide repeats was performed in the following genes: ATXN1 (SCA1), ATXN2 (SCA2), ATXN3 (SCA3), CACNA1A (SCA6), ATXN7 (SCA7), ATXN80S (SCA8), PPP2R2B (SCA12), TBP (SCA17), ATN1 (DRPLA). Afterwards, a search for FXTAS caused by premutation in the FMR1 gene was performed. Two hundred and sixty-nine subjects selected from the study group with 9 excluded types of SCAs were tested; a subgroup of 178 males aged 50 years was sorted out.

Results: Molecular analysis in 1385 individuals revealed SCA1 in 225, SCA2 in 56, SCA8 in 33, SCA17 in 4 subjects. SCA3, SCA6, SCA7, SCA12, and DRPLA were not detected. Within the subgroup aged>or=50 years with ataxia in whom 9 types of SCAs were excluded only one case of FXTAS was detected, which is 1/178 (0.56%), and within the group of males>or=70 years (n=19) one case was also found (5.26%).

Conclusions: The low frequency of FXTAS in the studied material probably results from the fact that the syndrome is much more common in elderly persons (penetrance of the pathogenic premutation gene is higher among elderly individuals).