The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease.
Huntington's disease (HD) is associated with the expansion of a CAG trinucleotide repeat in a novel gene. We have assessed 360 HD individuals from 259 unrelated families and found a highly significant correlation (r = 0.70, p = 10(-7)) between the age of onset and the repeat length, which accounts for approximately 50% of the variation in the age of onset. Significant associations were also found between repeat length and age of death and onset of other clinical features. Sib pair and parent-child analysis revealed that the CAG repeat demonstrates only mild instability. Affected HD siblings had significant correlations for trinucleotide expansion (r = 0.66, p < 0.001) which was not apparent for affected parent-child pairs.
Andrew
S E
SE
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Goldberg
Y P
YP
Kremer
B
B
Telenius
H
H
Theilmann
J
J
Adam
S
S
Starr
E
E
Squitieri
F
F
Lin
B
B
Kalchman
M A
MA
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005838:Genotype; D006801:Humans; D006816:Huntington Disease / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009679:Nuclear Family; D009838:Oligodeoxyribonucleotides; D010641:Phenotype; D012091:Repetitive Sequences, Nucleic Acid
D009838:Oligodeoxyribonucleotides; D004247:DNA