Intermediate CAG Repeats in Huntington’s Disease: Analysis of COHORT

Tremor and Other Hyperkinetic Movements

article

Ainhi D. Ha¹  Christopher A. Beck²  Joseph Jankovic¹ 

[1] Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine;Department of Biostatistics and Computational Biology, University of Rochester Medical Center

关键词: Huntington disease;    trinucleotide repeats;    chorea;    intermediate repeats;    genetic counseling;    huntingtin gene;   

DOI  :  10.5334/tohm.85

学科分类：社会科学、人文和艺术（综合）

来源: Ubiquity Press

【 摘 要 】

Background: There is emerging evidence that clinical and neuro-pathological manifestations of Huntington’s disease (HD) may occur in individuals with intermediate length cytosine-adenine-guanine (CAG) repeats (27–35 CAG repeats) in the Huntingtin ( HTT ) gene. We aim to further define the clinical characteristics of individuals who possess CAG repeat lengths in this range. Methods: Data from the Cooperative Huntington’s Observational Research Trial (COHORT) were analyzed. Participants were categorized according to the number of CAG repeats into normal (≤26), intermediate (27–35) and HD (≥36) groups. The motor, cognitive and behavioral scores on the Unified Huntington’s Disease Rating Scale (UHDRS) were compared between the intermediate and normal groups. Results: Of 1985 individuals affected by HD or with a family history of HD who were genotyped, 50 (2.5%) had their larger CAG repeat in the intermediate range. There were statistically significant differences in scores of some motor, cognitive, and behavioral domains of UHDRS at baseline between normal and intermediate length CAG repeats. Furthermore, a significantly greater number of subjects with CAG repeats in the intermediate range reported at least one suicide attempt compared to the normal group. Discussion: Our findings of motor, cognitive and behavioral abnormalities in individuals with intermediate CAG repeats suggest the presence of subtle, but relevant, disease manifestations in patients with intermediate CAG repeats. These results have important implications for the pathogenesis of the disease and genetic counseling.

【 授权许可】

CC BY