OBJECTIVES: We aimed to describe the clinical phenotype conferred by the intermediate-length huntingtin allele CAG repeat expansion in a population-based study. METHODS: The Prospective Huntington At Risk Observational Study (PHAROS) enrolled adults at risk for Huntington disease (HD). They were assessed approximately every 9 months with the Unified Huntington's Disease Rating Scale (UHDRS) by investigators unaware of participants' gene status. UHDRS scores were compared according to the Huntingtin gene CAG repeat number: expanded >36, intermediate 27-35, and nonexpanded controls <26. RESULTS: Fifty (5.1%) of the 983 participants had an intermediate allele (IA). They were similar to controls on UHDRS motor, cognitive, and functional measures, but significantly worse behaviorally on apathy and suicidal ideation. On 5 of the 9 other behavioral items and on total behavior, the IA group's scores were worse than those of controls and expanded participants, who themselves scored significantly worse than controls on 6 behavioral measures. Retention rates at 4 years were 48% for the IA group compared to 58% and 60% for the expanded and control groups. CONCLUSIONS: In a cohort at risk for HD, the IA was associated with significant behavioral abnormalities but normal motor and cognition. This behavioral phenotype may represent a prodromal stage of HD, with the potential for subsequent clinical manifestations, or be part of a distinct phenotype conferred by pathology independent of the CAG expansion length.
OBJECTIVES: We aimed to describe the clinical phenotype conferred by the intermediate-length huntingtin allele CAG repeat expansion in a population-based study. METHODS: The Prospective Huntington At Risk Observational Study (PHAROS) enrolled adults at risk for Huntington disease (HD). They were assessed approximately every 9 months with the Unified Huntington's Disease Rating Scale (UHDRS) by investigators unaware of participants' gene status. UHDRS scores were compared according to the Huntingtin gene CAG repeat number: expanded >36, intermediate 27-35, and nonexpanded controls <26. RESULTS: Fifty (5.1%) of the 983 participants had an intermediate allele (IA). They were similar to controls on UHDRS motor, cognitive, and functional measures, but significantly worse behaviorally on apathy and suicidal ideation. On 5 of the 9 other behavioral items and on total behavior, the IA group's scores were worse than those of controls and expanded participants, who themselves scored significantly worse than controls on 6 behavioral measures. Retention rates at 4 years were 48% for the IA group compared to 58% and 60% for the expanded and control groups. CONCLUSIONS: In a cohort at risk for HD, the IA was associated with significant behavioral abnormalities but normal motor and cognition. This behavioral phenotype may represent a prodromal stage of HD, with the potential for subsequent clinical manifestations, or be part of a distinct phenotype conferred by pathology independent of the CAG expansion length.
Authors: A Maat-Kievit; M Losekoot; H Van Den Boer-Van Den Berg; G J Van Ommen; M Niermeijer; M Breuning; A Tibben Journal: J Med Genet Date: 2001-04 Impact factor: 6.318
Authors: Nancy S Wexler; Judith Lorimer; Julie Porter; Fidela Gomez; Carol Moskowitz; Edith Shackell; Karen Marder; Graciela Penchaszadeh; Simone A Roberts; Javier Gayán; Denise Brocklebank; Stacey S Cherny; Lon R Cardon; Jacqueline Gray; Stephen R Dlouhy; Sandra Wiktorski; Marion E Hodes; P Michael Conneally; Jack B Penney; James Gusella; Jang-Ho Cha; Michael Irizarry; Diana Rosas; Steven Hersch; Zane Hollingsworth; Marcy MacDonald; Anne B Young; J Michael Andresen; David E Housman; Margot Mieja De Young; Ernesto Bonilla; Theresa Stillings; Americo Negrette; S Robert Snodgrass; Maria Dolores Martinez-Jaurrieta; Maria A Ramos-Arroyo; Jacqueline Bickham; Juan Sanchez Ramos; Frederick Marshall; Ira Shoulson; Gustavo J Rey; Andrew Feigin; Norman Arnheim; Amarilis Acevedo-Cruz; Leticia Acosta; Jose Alvir; Kenneth Fischbeck; Leslie M Thompson; Angela Young; Leon Dure; Christopher J O'Brien; Jane Paulsen; Adam Brickman; Denise Krch; Shelley Peery; Penelope Hogarth; Donald S Higgins; Bernhard Landwehrmeyer Journal: Proc Natl Acad Sci U S A Date: 2004-03-01 Impact factor: 11.205
Authors: Eric A Epping; Ji-In Kim; David Craufurd; Thomas M Brashers-Krug; Karen E Anderson; Elizabeth McCusker; Jolene Luther; Jeffrey D Long; Jane S Paulsen Journal: Am J Psychiatry Date: 2015-10-16 Impact factor: 18.112
Authors: Flor A Espinoza; Jessica A Turner; Victor M Vergara; Robyn L Miller; Eva Mennigen; Jingyu Liu; Maria B Misiura; Jennifer Ciarochi; Hans J Johnson; Jeffrey D Long; Henry J Bockholt; Vincent A Magnotta; Jane S Paulsen; Vince D Calhoun Journal: Brain Connect Date: 2018-03-08