[中国帕金森病患者SMPD1基因突变分析]
[Analysis of SMPD1 gene mutations in Chinese patients with Parkinson's disease].
作者信息
Song Na, Wang Wei, Chen Chao, Niu Jianyi, Guojin Yuxuan, Guo Cunju, Han Fabin
机构信息
Institute for Tissue Engineering and Regenerative Medicine, Liaocheng People's Hospital, Liaocheng University, Liaocheng, Shandong 252002, China.
出版信息
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2018 Jun 10;35(3):319-323. doi: 10.3760/cma.j.issn.1003-9406.2018.03.003.
OBJECTIVE
To explore the role of sphingomyedlin phosphodiesterase 1 (SMPD1) gene mutations in the pathogenesis of Parkinson's disease (PD).
METHODS
For 110 Chinese patients with PD, all exons of the SMPD1 gene were sequenced, and the results were compared with reference sequence from GenBank to identify possible mutations.
RESULTS
A novel heterozygous mutation Ex2:c.677C>A/p.P226Q (likely pathogenic) was identified in a patient, which resulted in substitution of Glutamic acid by Proline at position 226. In addition, two known single nucleotide polymorphisms (SNPs) Ex1:c.107T>C/p.V36A (benign) and Ex6:c.1522G>A/p.G508R (benign), and three previously reported SMPD1 mutations Ex2:c.T371T>G/p.L124R (uncertain significance), Ex2:c.636T>C/P.(=)(benign) and Ex6:c.1598C>T/p.P533L (uncertain significance) were identified. The novel p.P226Q mutation and p.P533L mutation were predicted to have a possibly damaging effect on the structure and function of SMPD1 protein, which in turn may lead to PD.
CONCLUSION
The mutation rate of the SMPD1 gene was 3.64% among Chinese PD patients. Genetic variants of SMPD1 may increase the risk of PD.
目的
探讨鞘磷脂磷酸二酯酶1（SMPD1）基因突变在帕金森病（PD）发病机制中的作用。
方法
对110例中国PD患者的SMPD1基因所有外显子进行测序，并将结果与GenBank中的参考序列进行比较，以确定可能的突变。
结果
在1例患者中鉴定出一种新的杂合突变Ex2:c.677C>A/p.P226Q（可能致病），该突变导致第226位谷氨酸被脯氨酸取代。此外，还鉴定出两个已知的单核苷酸多态性（SNP）Ex1:c.107T>C/p.V36A（良性）和Ex6:c.1522G>A/p.G508R（良性），以及三个先前报道的SMPD1突变Ex2:c.T371T>G/p.L124R（意义不确定）、Ex2:c.636T>C/P.(=)(良性)和Ex6:c.1598C>T/p.P533L（意义不确定）。新的p.P226Q突变和p.P533L突变预计会对SMPD1蛋白的结构和功能产生可能的破坏作用，进而可能导致PD。
结论
中国PD患者中SMPD1基因的突变率为3.64%。SMPD1的基因变异可能增加患PD的风险。
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