HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA.
University of Alabama in Huntsville, Huntsville, Alabama 35899, USA.
Cold Spring Harb Mol Case Stud. 2023 Jul 11;9(3). doi: 10.1101/mcs.a006271. Print 2023 Jun.
We collected and analyzed genomic sequencing data from individuals with clinician-diagnosed early-onset or atypical dementia. Thirty-two patients were previously described, with 68 newly described in this report. Of those 68, 62 patients self-reported white, non-Hispanic ethnicity and 6 reported as African-American, non-Hispanic. Fifty-three percent of patients had a returnable variant. Five patients harbored a pathogenic variant as defined by the American College of Medical Genetics criteria for pathogenicity. A polygenic risk score (PRS) was calculated for Alzheimer's patients in the total cohort and compared to the scores of a late-onset Alzheimer's cohort and a control set. Patients with early-onset Alzheimer's had higher non- PRSs than patients with late-onset Alzheimer's, supporting the conclusion that both rare and common genetic variation associate with early-onset neurodegenerative disease risk.
我们收集并分析了临床诊断为早发性或非典型痴呆症个体的基因组测序数据。本报告中描述了 32 例先前已描述的患者，以及 68 例新描述的患者。在这 68 例患者中，有 62 例患者自我报告为白人，非西班牙裔，6 例报告为非裔美国人，非西班牙裔。53%的患者有可检出的变异。5 名患者携带致病性变异，符合美国医学遗传学学院致病性定义标准。对总队列中的阿尔茨海默病患者计算了多基因风险评分（PRS），并与迟发性阿尔茨海默病队列和对照组的评分进行了比较。早发性阿尔茨海默病患者的非 PRS 高于迟发性阿尔茨海默病患者，这支持了这样一个结论，即罕见和常见的遗传变异都与早发性神经退行性疾病的风险相关。
