Searching for mutation in the JPH3, ATN1 and TBP genes in Polish patients suspected of Huntington's disease and without mutation in the IT15 gene.
OBJECTIVE
The aim of this study was to perform DNA analysis in patients with clinical diagnosis of Huntington's disease (HD) after molecular exclusion of HD and further molecular examinations for other neurodegenerative diseases such as Huntington's disease-like 2 (HDL-2; gene JPH3), dentatorubral pallidoluysian atrophy (DRPLA; gene ATN1) and spinocerebellar ataxia type 17 (SCA17; gene TBP).


METHODS
The material comprised 224 DNA samples isolated from peripheral blood from patients suspected of HD and 100 DNA samples from unaffected controls. The control group was used to determine the normal range of the number of CAG/CTG repeats in genes JPH3, ATN1 and TBP in the Polish population. Molecular analysis was carried out by PCR reaction, embracing microsatellite repeats in genes JPH3, ATN1 and TBP with specific, fluorescently labelled primers. PCR products were separated in polyacrylamide gels. The normal ranges of the number of repeats established for the control group in genes JPH3, ATN1 and TBP were 7-19, 9-27 and 29-45, respectively.


RESULTS
Molecular analysis of DNA from 224 individuals suspected of HD (117 women and 107 men) revealed one case of dynamic mutation - 55 CAG repeats - in the TBP locus (SCA17). No cases of DRPLA or HDL-2 were detected. The range of CAG/CTG repeats for the JPH3 gene in the patient group was 11-19, with the most common alleles containing 14 and 16 repeats. For the ATN1 gene in patients the range of 8-27 repeats was established and the most frequent allele with 16 triplets was present.


CONCLUSIONS
The study on 244 patients referred with the clinical diagnosis of HD and without mutation of the IT15 gene revealed one case of SCA17 but did not disclose the presence of two other diseases with a similar clinical manifestation: DRPLA and HDL2.
Sułek-Piatkowska
Anna
A
Instytut Psychiatrii i Neurologii, Zak(3)ad Genetyki, Al. Sobieskiego 9, 02-957 Warszawa. suleka@ipin.edu.pl
Krysa
Wioletta
W
Zdzienicka
Elzbieta
E
Szirkowiec
Walentyna
W
Hoffman-Zacharska
Dorota
D
Rajkiewicz
Marta
M
Fidziańska
Elzbieta
E
Kowalska
Grazyna
G
Zaremba
Jacek
J
D000180:Acrylic Resins; D000328:Adult; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D018895:Microsatellite Repeats; D008875:Middle Aged; D002527:Myoclonic Cerebellar Dyssynergia / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011044:Poland; D016133:Polymerase Chain Reaction; D012016:Reference Values; D020754:Spinocerebellar Ataxias / Q000235:genetics*; D035181:TATA-Box Binding Protein / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion
D000180:Acrylic Resins; C086055:HTT protein, human; D000071058:Huntingtin Protein; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D035181:TATA-Box Binding Protein; C509817:TBP protein, human; C095278:atrophin-1; C016680:polyacrylamide gels