汉族帕金森病患者SMPD1基因的突变分析  

Analysis of SMPDI gene mutations in Chinese patients with Parkinson＇s disease

作　　者：宋娜 王伟[1] 陈超[1] 牛建一[3] 郭金宇轩 郭存举 韩发彬[2] Song Na;Wang Wei;Chen Chao;Niu J ianyi;Guojin Yuxuan;Guo Cunju;Han Fabin(Institute for Tissue Engineering and Regenerative Medicine;Department of Neurology , Liaocheng People ＇ s Hospital, Liaocheng University, Liaocheng, Shandong 252002, China;Department of Neurology, Yidu Central Hospital, Wei fang, Shandong 262500, China)

机构地区：[1]聊城大学/聊城市人民医院组织工程与再生医学研究所,山东252002 [2]聊城大学/聊城市人民医院神经内科,山东252002 [3]山东省潍坊市益都中心医院神经内科,262500

出　　处：《中华医学遗传学杂志》2018年第3期319-323,共5页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金（81571241）;山东省医药卫生科技发展计划项目（2017WS504）

摘　　要：目的探讨帕金森病与SMPD1基因突变的相关性。方法对110例帕金森病患者进行SMPDl基因的全外显子测序分析，将测序结果与GenBank提供的标准序列进行对比，寻找基因序列的变异。结果在110例帕金森病患者中，1例患者具有新的杂合基因突变位点Ex2．c．677C〉A／p．P226Q（可能致病），所编码的第226位氨基酸由脯氨酸改变为谷氨酸。另外发现2个已知的单核苷酸多态性变异Exl：c．107T〉C／p．V36A（良性）、Ex6．c．1522G〉A／p．G508R（良性），以及3个已知变异Ex2：c．T371T〉G／p．L124R（意义不明）、Ex2：c.636T〉C／P．（一）（良性）、Ex6-c．1598C〉T／p．P533L（意义不明）。软件预测分析提示新的杂合突变P．P226Q和已知突变p．P533L很可能影响蛋白质的结构与功能，导致发病。结论在汉族帕金森病患者中SMPD1基因的突变率为3．64％，提示SMPDl基因的突变可能与帕金森病的发生相关。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 nueleofide polymorphisms （SNPs） Exl：c. 107T〉C/p. V36A （benign） and Ex6 ：e. 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 ： e. 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.

关 键 词：帕金森病 SMPD1基因 突变 测序 

分 类 号：R742.5[医药卫生—神经病学与精神病学]