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


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).
Rajkiewicz
Marta
M
Zakład Genetyki, Instytut Psychiatrii i Neurologii, ul. Sobieskiego 9, 02-957 Warsaw. rajkiewi@ipin.edu.pl
Sułek-Piatkowska
Anna
A
Krysa
Wioletta
W
Zdzienicka
Elzbieta
E
Szirkowiec
Walentyna
W
Zaremba
Jacek
J
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000706:statistics & numerical data; D042822:Genomic Instability; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011044:Poland / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D020754:Spinocerebellar Ataxias / Q000453:epidemiology / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; C497683:FMR1 protein, human