Improving diagnosis of Huntington's disease by analysis of an intragenic trinucleotide repeat expansion.
OBJECTIVE
To develop an accurate presymptomatic test for Huntington's disease.


METHODS
An improved polymerase chain reaction method was used to investigate the pattern of expansions of a CAG repeat sequence located in the 5' region of a gene recently found to produce the protein called Huntingtin. We documented the range of trinucleotide repeat expansions in the responsible gene in 82 affected individuals compared with 80 control subjects from a Western Australian population.


RESULTS
The number of expanded repeats ranged from 40 to 73 in affected individuals and from 13 to 38 in normal controls.


CONCLUSIONS
Polymerase chain reaction analysis of a CAG repeat sequence in the Huntington's disease gene clearly differentiated between normal and mutated alleles, providing an accurate diagnostic test for the disorder in individuals at risk. This predictive test has met with greater acceptance and demand than methods using family based linkage studies.
Beilby
J
J
Department of Clinical Biochemistry, Queen Elizabeth II Medical Centre, Nedlands, WA.
Chin
C Y
CY
Porter
I
I
Walpole
I R
IR
Goldblatt
J
J
D001483:Base Sequence; D016022:Case-Control Studies; D004247:DNA; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D006816:Huntington Disease / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D008297:Male; D008969:Molecular Sequence Data; D009710:Nucleotide Mapping / Q000379:methods*; D010342:Patient Acceptance of Health Care; D016133:Polymerase Chain Reaction / Q000379:methods*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014904:Western Australia / Q000453:epidemiology
D004247:DNA