Neuroimaging, genetic, and enzymatic study in a Japanese family with a GBA gross deletion
Neuroimaging, genetic, and enzymatic study in a Japanese family with a GBA gross deletion
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DOI：
10.1016/j.parkreldis.2018.11.028
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发表时间：
2019-04-01
影响因子：
4.1
通讯作者：
Takiyama, Yoshihisa
中科院分区：
文献类型：
--
作者：
Ichinose, Yuta;Ishiura, Hiroyuki;Takiyama, Yoshihisa
糖脑苷酶基因（GBA）变异与帕金森病（PD）和路易体痴呆（DLB）相关。然而，这些GBA变异疾病的分子机制尚不清楚。为了确定GBA缺失突变的影响，我们对一个GBA外显子3至11缺失的日本家庭进行了神经影像学、遗传学和酶学研究。方法：我们采用[I-123] FP-CIT SPECT和[I-123] n -异丙基-对碘安非他明SPECT (IMP-SPECT)，检测了2名GBA相关PD患者和9名未受影响的GBA基因杂合缺失突变的日本家庭个体（包括4名突变携带者）白细胞中GBA的表达和葡萄糖脑苷酶（GCase）活性。结果：2例PD患者和4例临床未受影响的携带者中的2例显示[I-123] FP-CIT摄取减少。IMP-SPECT表现与1例DLB相似。当我们将GBA突变的PD患者与临床未受影响的携带者进行比较时，PD的发展与GBA或GCase活性的表达水平之间的相关性较差。结论：我们证实了GBA基因的大缺失突变，该突变可能与该家族PD或[I-123] FP-CIT降低有关。然而，由于我们无法得出GCase活性降低是否与PD发病直接相关的结论，因此需要对该家族进行纵向随访。
Introduction: Glucocerebrosidase gene (GBA) variants are associated with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The molecular mechanisms underlying these diseases with GBA variants, however, are not well understood. In order to determine the effect of a deletion mutation in GBA, we performed a neuroimaging, genetic, and enzymatic study in a Japanese family with a gross deletion of exons 3 to 11 in GBA.Methods: We performed [I-123] FP-CIT SPECT and [I-123] N-isopropyl-p-iodoamphetamine SPECT (IMP-SPECT), and determined GBA expression and glucocerebrosidase (GCase) activity in leukocytes in two GBA-associated PD patients and nine unaffected individuals (including four mutation carriers) in a Japanese family with a heterozygous gross deletion mutation in the GBA gene.Results: The two PD patients and two of the four clinically unaffected carriers showed decreased [I-123] FP-CIT uptake. IMP-SPECT showed a pattern like that in DLB in one patient. When we compared PD patients with GBA mutations with clinically unaffected carriers, there was a poor correlation between the development of PD and the expression level of GBA or GCase activity.Conclusion: We confirmed the gross deletion mutation in the GBA gene, which appeared to be associated with the PD or reduced [I-123] FP-CIT in this family. However, since we cannot conclude whether a reduction of GCase activity is directly correlated with the pathogenesis of PD or not, longitudinal follow-up of this family is needed.