Bardet-Biedl综合征—家系致病基因筛查

发布时间：2018-12-12 03:10

【摘要】：[目的] 应用候选基因筛查方法对湖北省襄樊市一Bardet-Biedl综合征家系进行致病基因排除定位。 [材料和方法] 1.通过家系调查收集家系临床资料。 2.抽取家系成员外周血并提取全血基因组DNA。 3.查阅文献及网络数据库,确定已知的发病率高的BBS致病基因为候选基因。 4.对于所选取的候选基因BBS1、BBS2、BBS4、MKKS/BBS6、BBS7、 TTC8/BBS8、B1/BBS9、BBS10、BBS12、MKS1/BBS13基因所有外显子设计引物,将先证者基因组DNA进行PCR扩增后直接测序,通过与网络数据库进行比对,明确有无突变。 [结果] 家系临床研究结果：YFM家系疾病为确诊的Bardet-Biedl综合征,为常染色体隐性遗传病。对于先证者BBS1、BBS2、MKKS/BBS6、BBS7、TTC8/BBS8、B1/BBS9、 BBS10、BBS12、MKS1/BBS13基因所有外显子编码区直接测序结果显示,未发现致病性突变。先证者BBS4基因第13外显子编码区有一杂合性突变导致BBS4蛋白发生I354T突变,但经生物信息学方法预测,此突变对于蛋白质结构功能影响不大。且该突变不与家系中患者共分离,亦未发现纯合性突变或复合杂合性突变,故不是YFM家系的致病性突变。 [结论] YFM家系致病基因可能为罕见基因或一个新的基因。
[Abstract]:[objective] to locate the pathogenicity gene of a Bardet-Biedl syndrome family in Xiangfan, Hubei province by candidate gene screening method. [materials and methods] 1. Family clinical data were collected through family investigation. 2. Extraction of Peripheral Blood from Family members and extraction of Genomic DNA. from whole Blood 3. Literature and web databases were reviewed to identify known BBS pathogenic genes as candidate genes. 4. Primers were designed for all exons of the selected candidate gene BBS1,BBS2,BBS4,MKKS/BBS6,BBS7, TTC8/BBS8,B1/BBS9,BBS10,BBS12,MKS1/BBS13 gene. The proband genomic DNA was amplified by PCR and sequenced directly. By comparing with the network database, it is clear whether there is a mutation. Results: YFM family disease was diagnosed as Bardet-Biedl syndrome and autosomal recessive disease. Direct sequencing of all exons of the probands BBS1,BBS2,MKKS/BBS6,BBS7,TTC8/BBS8,B1/BBS9, BBS10,BBS12,MKS1/BBS13 gene showed that no pathogenicity mutation was found. A heterozygous mutation in the coding region of exon 13 of the proband BBS4 gene led to the I354T mutation of BBS4 protein, but this mutation had little effect on the protein structure and function by bioinformatics method. The mutation was not isolated from the patients in the family, nor was homozygous mutation or compound heterozygosity mutation, so it was not the pathogenicity mutation of YFM pedigree. [conclusion] the pathogenic gene of YFM family may be a rare gene or a new gene.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R596;R771.3

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