Moran Eileen E, Bressman Susan B, Ortega Roberto A, Raymond Deborah, Nichols William C, Palmese Christina A, Elango Sonya, Swan Matthew, Shanker Vicki, Perera Imali, Wang Cuiling, Zimmerman Molly E, Saunders-Pullman Rachel
Department of Psychology, Fordham University, Bronx, NY, United States.
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States.
Front Neurol. 2021 Feb 26;12:635958. doi: 10.3389/fneur.2021.635958. eCollection 2021.
Mutations and variants in the glucocerebrosidase () gene are among the most common genetic risk factors for the development of Parkinson's disease (PD). Yet, penetrance is markedly reduced, and less is known about the burden of carrying a single mutation among those without diagnosed PD. Motor, cognitive, psychiatric, and olfactory functioning were assessed in 30 heterozygous mutation carriers without PD (the majority of whom had mild mutations) and 49 non-carriers without PD. Study focus was on domains affected in mutation carriers with PD, as well as those previously shown to be abnormal in mutation carriers without PD. mutation carriers showed poorer performance on the Stroop interference measure of executive functioning when controlling for age. There were no group differences in verbal memory, Montreal Cognitive Assessment (MoCA), overall motor score, or presence of REM sleep behavior disorder or depression. Although total olfaction scores did not differ, mutation carriers with hyposmia had lower global cognition scores than those without hyposmia. As anticipated by the low penetrance of mutations, these findings suggest that pre-manifest non-motor or motor features of PD may not present in most mutation carriers. However, there is support that there may be a subtle difference in executive functioning among some non-manifesting heterozygous mutation carriers, and, combined with olfaction, this may warrant additional scrutiny as a potential biomarker for pre-manifest and pre-clinical related PD.
葡萄糖脑苷脂酶（）基因突变和变异是帕金森病（PD）发生发展最常见的遗传风险因素之一。然而，其外显率明显降低，对于未被诊断为PD的单基因突变携带者的负担了解较少。对30名未患PD的杂合基因突变携带者（其中大多数为轻度基因突变）和49名未患PD的非携带者进行了运动、认知、精神和嗅觉功能评估。研究重点是PD基因突变携带者中受影响的领域，以及先前在未患PD的基因突变携带者中显示异常的领域。在控制年龄后，基因突变携带者在执行功能的Stroop干扰测试中表现较差。在言语记忆、蒙特利尔认知评估（MoCA）、总体运动评分、快速眼动睡眠行为障碍或抑郁的存在方面，两组之间没有差异。虽然总嗅觉评分没有差异，但嗅觉减退的基因突变携带者的整体认知评分低于无嗅觉减退的携带者。正如基因突变低外显率所预期的那样，这些发现表明，大多数基因突变携带者可能不会出现PD的临床前期非运动或运动特征。然而，有证据支持，一些未表现出症状的杂合基因突变携带者在执行功能方面可能存在细微差异，并且，结合嗅觉来看，这可能值得作为PD临床前期和临床前相关的潜在生物标志物进行额外的仔细检查。
