title: Mosaicism of the CAG repeat sequence in the Huntington disease gene in a pair of monozygotic twins.
abstract: We report on a pair of monozygotic twins belonging to a family segregating Huntington disease (HD). In routine DNA analysis of blood cells, they displayed three alleles of the CAG repeat sequence in the HD gene. Two different cell lines, carrying the normal allele together with either an expanded allele with 47 CAGs or an intermediate allele with 37 CAGs, were detected in blood and buccal epithelium from both twins. To our knowledge, this is the first case described of HD gene CAG repeat length mosaicism in blood cells. Haplotype analysis established that the 37 CAG allele most likely arose by contraction of the maternal 47 CAG allele. The contraction must have taken place postzygotically, possibly at a very early stage of development, and probably before separation of the twins. One of the twins has presented symptoms of HD for 4 years; his skin fibroblasts and hair roots carried only the cell line with the 47 CAG repeat allele. The other twin, who is without symptoms at present, displayed mosaicism in skin fibroblasts and hair roots. If the proportion of the two cell lines in the brain of each twin resembles that of their hair roots (another tissue originating from the ectoderm), the mosaicism in the unaffected twin would mean that only a part of his brain cells carried the expanded allele, which could explain why he, in contrast to his brother, has no symptoms at this time.
authors.affiliation: Institute of Medical Biochemistry and Genetics, Section of Neurogenetics, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Nørremølle
authors.forename: Lis
authors.initials: L
authors.lastname: Hasholt
authors.forename: Cathrine Bie
authors.initials: CB
authors.lastname: Petersen
authors.forename: Hans
authors.initials: H
authors.lastname: Eiberg
authors.forename: Steen G
authors.initials: SG
authors.lastname: Hasselbalch
authors.forename: Peter
authors.initials: P
authors.lastname: Gideon
authors.forename: Jørgen E
authors.initials: JE
authors.lastname: Nielsen
authors.forename: Sven Asger
authors.initials: SA
authors.lastname: Sørensen
mesh_terms: D000328:Adult; D004247:DNA / Q000097:blood / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005347:Fibroblasts / Q000378:metabolism; D006197:Hair / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000175:diagnosis / Q000235:genetics; D008297:Male; D009030:Mosaicism; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012867:Skin / Q000166:cytology / Q000378:metabolism; D013094:Spermatozoa / Q000378:metabolism; D018911:Trinucleotide Repeats / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D004247:DNA