Limited expansion of the (CAG)n repeat of the Huntington gene: a premutation (?).
Huntington's disease (HD) is an autosomal dominant disorder with choreic movements, psychiatric manifestations and cognitive dysfunction. Recently the IT15 gene on chromosome 4p has been identified containing an unstable and expanded trinucleotide repeat in patients with HD. We report on the characteristics of this repeat in 248 individuals from 41 Belgian HD families. The length of the expanded repeat was defined precisely and reproducibly on an ALF sequencer and correlated well with the age of onset (r = -0.72). Paternal transmission of the expanded repeat resulted on average in a significantly longer repeat length (+2.79 repeats) than maternal transmission (-0.29 repeats). (CAG)n repeat of a premutation (?) size was observed in this population with subsequent expansion in the disease range. Presymptomatic or prenatal testing using only linked markers may be problematic in these cases.
Legius
E
E
Center for Human Genetics, University of Leuven, Belgium.
Cuppens
H
H
Dierick
H
H
Van Zandt
K
K
Dom
R
R
Fryns
J P
JP
Evers-Kiebooms
G
G
Decruyenaere
M
M
Demyttenaere
K
K
Marynen
P
P
D000328:Adult; D017668:Age of Onset; D000368:Aged; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005220:Fathers; D005260:Female; D015870:Gene Expression; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D006816:Huntington Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009035:Mothers; D009154:Mutation; D012091:Repetitive Sequences, Nucleic Acid; D012737:Sex Factors
D017931:DNA Primers; D004247:DNA