一例Bardet-Biedl综合征患者MKKS基因新变异的遗传学分析  

Genetic analysis of novel MKKS variants in a Chinese patient with Bardet-Biedl syndrome

作　　者：李昊 胡章学[1] Li Hao;Hu Zhangxue(Department of Nephrology,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China)

机构地区：[1]四川大学华西医院肾脏内科,成都610041

出　　处：《中华医学遗传学杂志》2022年第7期754-758,共5页Chinese Journal of Medical Genetics

基　　金：成都市科技局项目(2021-YF05-00993-SN)。

摘　　要：目的对一例Bardet-Biedl综合征(Bardet-Biedl syndrome,BBS)患者进行遗传学分析。方法收集患者的临床资料,对患者进行纤毛病相关基因的高通量测序,并对候选变异进行生物信息学分析。结果在先证者中检出MKKS基因c.635C>T(p.Ser212Phe)和c.1664C>G(p.Thr555Arg)杂合变异及TMEM67基因c.2498T>C(p.Ile833Thr)杂合变异。其母亲携带MKKS基因c.635C>T(p.Ser212Phe)杂合变异,而未携带MKKS基因c.1664C>G(p.Thr555Arg)及TMEM67基因c.2498T>C(p.Ile833Thr)变异。上述3个变异位点所对应的氨基酸序列在不同物种中高度保守。结论MKKS基因c.635C>T(p.Ser212Phe)和c.1664C>G(p.Thr555Arg)复合杂合变异可能为患者的遗传学病因。TMEM67基因c.2498T>C(p.Ile833Thr)杂合变异对其疾病表型是否具有修饰作用还有待进一步的研究。Objective To explore the genetic basis of a Chinese patient with Bardet-Biedl syndrome(BBS).Methods Clinical data of the patient was analyzed.Next-generation sequencing was carry out to screen pathogenic variants,and candidate variants were verified by Sanger sequencing and subjected to bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics.Results Next-generation sequencing revealed that the proband has harbored two pathogenic variants of the MKKS gene(c.635C>T and c.1664C>G)and one likely pathogenic variant of the TMEM67 gene(c.2498T>C).Sanger sequencing of the proband and her mother confirmed that the proband has harbored two compound heterozygous MKKS variants and a heterozygous TMEM67 variant.Both of the MKKS variants were previously unreported and located in a highly conserved domain and predicted to be disease-causing by bioinformatic analysis.Conclusion The two novel MKKS/BBS6 variants probably underlay the BBS in the proband.The TMEM67 variant may have an epistatic effect on mutations of BBS-associated loci.

关 键 词：BARDET-BIEDL综合征 MKKS基因 TMEM67基因 纤毛病 三等位基因遗传 

分 类 号：R596[医药卫生—内科学]