CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

Lee, J-M; Ramos, EM; Lee, J-H; Gillis, T; Mysore, JS; Hayden, MR; Warby, SC; Morrison, P; Nance, M; Ross, CA; Margolis, RL; Squitieri, F; Orobello, S; Di Donato, S; Gomez-Tortosa, E; Ayuso, C; Suchowersky, O; Trent, RJA; McCusker, E; Novelletto, A; Frontali, M; Jones, R; Ashizawa, T; Frank, S; Saint-Hilaire, MH; Hersch, SM; Rosas, HD; Lucente, D; Harrison, MB; Zanko, A; Abramson, RK; Marder, K; Sequeiros, J; Paulsen, JS; Landwehrmeyer, GB; Myers, RH; MacDonald, ME; Gusella, JF; REGISTRY study of the European Huntington's Disease Network,; Vandenberghe, Wim

doi:10.1212/WNL.0b013e318249f683

CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

Author:

Lee, J-M

Ramos, EM ; Lee, J-H ; Gillis, T ; Mysore, JS ; Hayden, MR ; Warby, SC ; Morrison, P ; Nance, M ; Ross, CA ; Margolis, RL ; Squitieri, F ; Orobello, S ; Di Donato, S ; Gomez-Tortosa, E ; Ayuso, C ; Suchowersky, O ; Trent, RJA ; McCusker, E ; Novelletto, A ; Frontali, M ; Jones, R ; Ashizawa, T ; Frank, S ; Saint-Hilaire, MH ; Hersch, SM ; Rosas, HD ; Lucente, D ; Harrison, MB ; Zanko, A ; Abramson, RK ; Marder, K ; Sequeiros, J ; Paulsen, JS ; Landwehrmeyer, GB ; Myers, RH ; MacDonald, ME ; Gusella, JF ; REGISTRY study of the European Huntington's Disease Network, ; Vandenberghe, Wim

Keywords:

Adult, Age of Onset, Alleles, Female, Genotype, Humans, Huntington Disease, Male, Trinucleotide Repeat Expansion, Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences & Neurology, TRINUCLEOTIDE REPEAT, OF-ONSET, HOMOZYGOSITY, MUTATION, ALLELE, LENGTH, HD, PREDICT-HD study of the Huntington Study Group (HSG), REGISTRY study of the European Huntington's Disease Network, HD-MAPS Study Group, COHORT study of the HSG, 1103 Clinical Sciences, 1109 Neurosciences, 1702 Cognitive Sciences, Neurology & Neurosurgery, 3202 Clinical sciences, 3209 Neurosciences

Abstract:

Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs.