The risk of Parkinson's disease in type 1 Gaucher disease.
The risk of Parkinson's disease in type 1 Gaucher disease.
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DOI：
10.1007/s10545-010-9055-0
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发表时间：
2010-04
影响因子：
4.2
通讯作者：
Mistry, Pramod K.
中科院分区：
文献类型：
--
作者：
Bultron, Gilberto;Kacena, Katherine;Pearson, Daniel;Boxer, Michael;Yang, Ruhua;Sathe, Swati;Pastores, Gregory;Mistry, Pramod K.
在戈谢病中，由于GBA1基因突变导致溶酶体糖脑苷酶缺陷导致单核吞噬细胞中糖脑苷的溶酶体积累和多系统表型。对一些非神经病变1型戈谢病（GD1）及其一级亲属患者帕金森病发生的观察导致GBA1杂合突变被确定为特发性帕金森病（PD）的遗传危险因素。然而，已知GD1患者患PD的风险大小尚未确定，也不清楚GD1/PD是否代表具有独特基因型/表型特征的GD1的特定亚表型。我们估计了444名连续评估的GD1患者与普通人群的PD风险。在12年的随访期间，11名患者患上了帕金森综合症。GD1中PD与一般人群的校正终生风险比为21.4[95%置信区间（95% CI） 10.7-38.3]，男性风险高于女性。在我们的队列中，GD1/帕金森病表型（GD1/PD）的特点是GD1严重程度评分较高，这是由于无血管性骨坏死的发生率较高。PD的临床谱系从轻度到潜在的危及生命的疾病不等。除1例外，所有GD1/PD表型患者至少有一个N370S GBA1等位基因。总之，与一般人群相比，GD1患者一生中患PD的风险增加了近20倍。
In Gaucher disease, defective lysosomal glucocerebrosidase due to mutations in the GBA1 gene results in lysosomal accumulation of glucocerebroside in mononuclear phagocytes and a multisystemic phenotype. Observations of occurrence of Parkinson's disease in some patients with non-neuronopathic type 1 Gaucher disease (GD1) and their first degree relatives has led to the identification of GBA1 heterozygous mutations as a genetic risk factor for idiopathic Parkinson's disease (PD). However, the magnitude of risk of PD in patients with known GD1 has not been determined, and it is not known whether GD1/PD represents a specific sub-phenotype of GD1 with distinctive genotype/phenotype characteristics. We estimated the risk of PD in a cohort of 444 consecutively evaluated patients with GD1 compared to that in the general population. Eleven patients developed parkinsonian syndrome during a 12-year follow-up period. The adjusted life-time risk ratio of PD in GD1 compared to that in the general population was 21.4 [95% confidence interval (95% CI) 10.7–38.3], with a higher risk in men compared to women. In our cohort, GD1/Parkinson's disease phenotype (GD1/PD) was characterized by higher GD1 severity score, due to higher incidence of avascular osteonecrosis. The clinical spectrum of PD varied from mild to potentially life-threatening disease. All but one patient with GD1/PD phenotype had at least one N370S GBA1 allele. In conclusion, compared to the general population, patients with GD1 have an almost 20-fold increased life-time risk of developing PD.
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影响因子：
--
作者：
Mitsui, Jun;Mizuta, Ikuko;Tsuji, Shoji
通讯作者：
Tsuji, Shoji
影响因子：
3.8
作者：
Mistry, PK;Sirrs, S;Goldman, ME
通讯作者：
Goldman, ME
影响因子：
8.6
作者：
Clark, LN;Nicolai, A;Marder, K
通讯作者：
Marder, K
影响因子：
3.8
作者：
Beutler, Ernest
通讯作者：
Beutler, Ernest
DOI：
10.1089/gte.1997.1.5
发表时间：
1997-06-01
期刊：
GENETIC TESTING
影响因子：
--
作者：
Grabowski, GA
通讯作者：
Grabowski, GA