中国南方人群遗传性痉挛性截瘫SLC33A1基因的突变检测

Mutation Detection of SLC33A1 in Southern Chinese Hereditary Spastic Paraplegias Patients

【目的】SLC33A1基因已被报道是我国北方一个HSP家系的致病基因,但研究未发现在欧洲的HSP患者中有该基因的突变。本研究的目的是检测SLC33A1是否为中国南方人群中遗传性痉挛性截瘫患者的致病性基因之一。【方法】对收集到的70例中国南方散发遗传性痉挛性截瘫的患者,提取基因组DNA,并进行SLC33A1基因所有编码外显子及外显子-内含子交界区域的直接测序;鉴定所发现的遗传变异,并同我们所收集到的57例无血缘关系的正常人进行比对,以及生物信息学分析。【结果】我们只发现SLC33A1基因区域的8个已存在于数据库中的单核苷酸多态性,未发现任何致病性突变。【结论】与国外学者的报道相符合,我们的70例中国南方HSP病人中没有SLC33A1所导致的病人,故SLC33A1对HSP的致病性需要进一步的核实、研究。

[Objective]SLC33A1 has been reported to be the causal gene in a Northern Chinese hereditary spastic paraplegias family.However the gene＇s causality has not been confirmed,as a group of German scientists has ruled it out in their cohort.The aim of this study is to detect the possible mutation（s） of the SLC33A1 gene in a cohort of the Southern Chinese.[Methods]Genomic DNA was extracted from 70 independent HSP patients and 57 healthy unrelated healthy subjects.Direct sequencing was performed in the coding regions and intron-exon boundaries of the SLC33A1 gene on the PCR products.Variations identified were compared with the results from the control subjects and our bioinformatics searched in the dbSNP and 1000 genome project.[Results]Besides the eight known single nucleotide polymorphisms already deposited in the databases,we did not find any mutation in our patients.[Conclusions]The causality of SLC33A1 in HSP needs further investigation and confirmation.