Dagan Efrat, Schlesinger Ilana, Kurolap Alina, Ayoub Mareemar, Nassar Maria, Peretz-Aharon Judith, Gershoni-Baruch Ruth
Department of Nursing, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel.
Dement Geriatr Cogn Disord. 2016;42(1-2):1-6. doi: 10.1159/000447450. Epub 2016 Jul 23.
BACKGROUND/AIM: Parkinson's disease (PD) is associated with mutations in LRRK2, GBA, and SMPD1 genes. We describe the clinical characteristics of PD patients related to their carrier status of the Ashkenazi founder mutations in the aforementioned genes.
Ashkenazi PD patients (n = 270) were recruited following informed consent, and tested for the founder Ashkenazi mutations in the above genes. Clinical characteristics were compared between carriers and noncarriers. Homozygotes for mutations in GBA or LRRK2, and those who carried mutations in two causative genes were excluded from the analysis.
Five (1.85%), 54 (20%), and 22 (8.1%) PD patients carried mutations in SMPD1, GBA or LRRK2, respectively. By post hoc Bonferroni analysis, GBA carriers were singled at a significantly earlier age at diagnosis compared to noncarriers (58.06 ± 10.84 and 62.65 ± 10.86 years, respectively; p = 0.036), and due to bilateral manifestation at diagnosis compared to all other PD groups (n = 8, 15.7% compared to n = 2, 1.1%, respectively; p < 0.001). Other clinical manifestations were comparable between groups.
Although only GBA mutation carriers, compared to noncarriers, reached statistical significance regarding age at diagnosis, it appears that LRRK2 and SMPD1 mutation carriers may reach significance with larger group numbers.
背景/目的：帕金森病（PD）与亮氨酸丰富重复激酶2（LRRK2）、β-葡萄糖脑苷脂酶（GBA）和鞘磷脂磷酸二酯酶1（SMPD1）基因的突变有关。我们描述了与上述基因中阿什肯纳兹始祖突变携带者状态相关的帕金森病患者的临床特征。
在获得知情同意后招募阿什肯纳兹帕金森病患者（n = 270），并对上述基因中的始祖阿什肯纳兹突变进行检测。比较携带者和非携带者的临床特征。分析中排除了GBA或LRRK2突变的纯合子以及携带两种致病基因突变的患者。
分别有5名（1.85%）、54名（20%）和22名（8.1%）帕金森病患者携带SMPD1、GBA或LRRK2突变。通过事后Bonferroni分析，与非携带者相比，GBA突变携带者的诊断年龄显著更早（分别为58.06±10.84岁和62.65±10.86岁；p = 0.036），且与所有其他帕金森病组相比，诊断时双侧受累的比例更高（分别为8例，15.7%和2例，1.1%；p < 0.001）。其他临床表现各组间相当。
虽然只有GBA突变携带者与非携带者相比，在诊断年龄方面具有统计学意义，但似乎LRRK2和SMPD1突变携带者在样本量更大时可能具有统计学意义。
