부산대학교 도서관

Background: Carriers of small cytosine‐adenine‐guanine (CAG) repeats below 39 in the HTT gene are traditionally associated with milder Huntington's disease, but their clinical profile has not been extensively studied. Objective: To study the phenotype of CAG36‐38 repeat carriers. Methods: We included 35 patients and premanifest carriers of CAG36‐38 repeats. We compared clinical and neuropsychological profiles of 11 CAG36‐38 patients with 11 matched CAG40‐42 patients. In addition, we analyzed 243 CAG36‐38 individuals from the ENROLL study to complete the phenotype description. Results: Global cognitive efficiency and performance in different cognitive subdomains were similar in small CAG36‐38 and typically CAG40‐42 expanded individuals. Chorea as the first symptom was significantly less frequent for CAG36‐38 patients (P = 0.04) despite similar total motor scores at first visit. Total motor score at last visit was significantly lower in CAG36‐38 carriers (P = 0.003). The similar cognitive and different motor profile of CAG36‐38 (n = 243) and CAG40‐42 (n = 4675) carriers was confirmed in the ENROLL database. Additionally, clinicians were significantly less confident in diagnosing Huntington's disease (P = 2.4e−8) and diagnosis happened significantly later in CAG36‐38 (P = 2.2e−6) despite a similar age at symptom onset (P = 0.29). Conclusions: We showed that small CAG36‐38 expansion carriers had a similar cognitive profile to those with the more common CAG40‐42 expansions. These individuals may evade molecular diagnosis because of the absence of chorea rather than because of a low penetrance of symptoms. This finding should encourage neurologists to consider Huntington's disease in cognitively impaired elderly patients without typical chorea and anticipate consequences for genetic counseling in their offspring. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]