Lesch-Nyhan综合征一个家系的遗传学分析  

Genetic analysis of a Chinese pedigree with Lesch-Nyhan syndrome

作　　者：王杜娟 赵晶晶[1] 滕娟 李文 赵向宇 李琳[2] Wang Dujuan;Zhao Jingjing;Teng Juan;Li Wen;Zhao Xiangyu;Li Lin(Department of Gynecology and Obstetrics,Linyi People′s Hospital,Linyi,Shandong 276003,China;Department of Genetic Laboratory,Linyi People′s Hospital,Linyi,Shandong 276003,China;Department of Reproductive Medicine,Linyi,Shandong 276003,China)

机构地区：[1]临沂市人民医院妇产科,临沂276003 [2]临沂市人民医院遗传检验科,临沂276003 [3]临沂市人民医院生殖医学科,临沂276003

出　　处：《中华医学遗传学杂志》2023年第6期723-726,共4页Chinese Journal of Medical Genetics

基　　金：山东省自然科学基金(ZR2020QH047);山东省重点研发计划(2017GSF218072)。

摘　　要：目的探讨1个Lesch-Nyhan综合征家系的遗传学病因。方法选取2022年2月10日在临沂市人民医院接受遗传咨询的1个Lesch-Nyhan综合征家系作为研究对象。收集先证者的临床资料及家族史,对先证者及其父母进行家系全外显子组测序(trio-WES),对候选变异进行Sanger测序家系验证。结果先证者主要表现为精神及行为异常、运动发育迟缓和高尿酸血症,其表弟存在类似症状。基因检测发现先证者及其表弟均携带既往未见报道的HPRT1基因c.385-1G>C半合子变异,先证者母亲、外祖母、大姨、小姨、表妹均携带HPRT1基因c.385-1G>C杂合变异,家系中表型正常的男性该位点均为野生型,符合X连锁隐性遗传的特征。结论HPRT1基因c.385-1G>C半合子变异可能是该Lesch-Nyhan综合征家系的遗传学病因。Objective To explore the genetic etiology for a Chinese pedigree affected with Lesch-Nyhan syndrome.Methods Members of the pedigree who had visited the Genetic Counseling Clinic of Linyi People′s Hospital on February 10,2022 were selected as the study subjects.Clinical data and family history of the proband were collected,and trio-whole exome sequencing(trio-WES)was carried out for the proband and his parents.Candidate variants were verified by Sanger sequencing.Results Trio-WES revealed that both the proband and his cousin brother had harbored a hemizygous c.385-1G>C variant in intron 4 of the HPRT1 gene,which was unreported previously.A heterozygous c.385-1G>C variant of the HPRT1 gene was also found in the proband′s mother,grandmother,two aunts,and a female cousin,whilst all phenotypically normal males in his pedigree were found to have a wild type for the locus,which has conformed to an X-linked recessive inheritance.Conclusion The heterozygous c.385-1G>C variant of the HPRT1 gene probably underlay the Lesch-Nyhan syndrome in this pedigree.

关 键 词：高尿酸血症 Lesch-Nyhan综合征 HPRT1基因 基因变异 

分 类 号：R596[医药卫生—内科学]