婴儿神经轴索营养不良致病基因PLA2G6突变分析  

Mutational analysis of the pathogenic gene PLA2G6 in infantile neuroaxonal dystrophy

作　　者：常世雪 李翠[1,2] 杨溪玲 甄帅 赵明刚[1,2] 李旭 赵乐[1] CHANG Shixue;LI Cui;YANG Xiling;ZHEN Shuai;ZHAO Minggang;LI Xu;ZHAO Le(Center for Translational Medicine,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China;Genetic Disease Diagnosis Center of Shaanxi Province,Xi'an 710061,China;Department of Medical Genetics and Developmental Biology,School of Basic Medical Sciences,Air Force Medical University,Xi'an 710032,China)

机构地区：[1]西安交通大学第一附属医院转化医学中心,陕西西安710061 [2]陕西省遗传疾病诊断中心,陕西西安710061 [3]空军军医大学基础医学院医学遗传与发育生物学教研室,陕西西安710032

出　　处：《空军军医大学学报》2024年第6期650-656,共7页Journal of Air Force Medical University

基　　金：陕西省自然科学基础研究计划项目(2022JQ-533)。

摘　　要：目的探讨婴儿神经轴索营养不良(INAD)PLA2G6基因突变的致病特点,丰富INAD的基因突变谱,为INAD相关遗传咨询提供依据。方法收集1例先证者的家系相关临床资料,采用三人家系全外显子组测序对先证者及其父母进行测序分析,筛选可能的致病突变位点,Sanger测序验证突变位点,结合生物信息学分析对突变位点的致病性进行预测,最后通过羊水穿刺检查为孕妇提供产前诊断。结果全外显子测序结果显示临床表现为精神运动发育倒退的先证者为PLA2G6基因c.1A>G(p.M1?)和c.2242G>A(p.A748T)复合杂合突变,其父亲为c.1A>G(p.M1?)杂合突变携带者,母亲为c.2242G>A(p.A748T)杂合突变携带者。根据美国医学遗传学与基因组学学会变异评级相关指南,c.1A>G(p.M1?)为致病性突变,c.2242G>A(p.A748T)为意义未明突变。产前诊断胎儿为c.1A>G(p.M1?)杂合突变携带者,现该孕妇已足月顺产一男活婴,产后随访7个多月生长状况良好。结论PLA2G6基因c.1A>G(p.M1?)和c.2242G>A(p.A748T)复合杂合突变为该先证者患INAD的遗传病因,其中c.2242G>A(p.A748T)为新发现的变异位点,这扩大了INAD的基因突变图谱,全外显子测序数据为该家系提供了精准的遗传咨询和产前诊断。Objective To investigate the pathogenic characteristics in PLA2G6 gene mutation of infantile neuroaxonal dystrophy(INAD),enrich the gene mutation spectrum of INAD,and provide a theoretical basis for INAD-related genetic counseling.Methods Clinical data related to the family of a proband were collected.Whole exome sequencing followed by Sanger sequencing was performed for the proband and her parents to screen for possible pathogenic mutation sites.The mutation sites were verified by Sanger sequencing,and the pathogenicity of the mutation sites was predicted by combining bioinformatics analysis.Finally,prenatal diagnosis was provided for the pregnant woman through amniocentesis.Results Whole exome sequencing results showed that the proband with clinical manifestations of psychomotor development regression was compound heterozygous mutations in the PLA2G6 gene c.1A>G(p.M1?)and c.2242G>A(p.A748T),with her father being a carrier of c.1A>G(p.M1?)heterozygous mutation,and her mother a carrier of c.2242G>A(p.A748T)heterozygous mutation.According to the American College of Medical Genetics and Genomics guidelines for variant rating,c.1A>G(p.M1?)was a pathogenic mutation,while c.2242G>A(p.A748T)was a variant of uncertain significance.Prenatal diagnosis showed that the fetus was a carrier of the c.1A>G(p.M1?)heterozygous mutation.The pregnant woman later gave birth to a live boy at full term,and the baby had normal growth and development during the follow-up of 7 months after delivery.Conclusion The compound heterozygous mutations c.1A>G(p.M1?)and c.2242G>A(p.A748T)in PLA2G6 gene are the pathogenic mutations of the proband with INAD,of which c.2242G>A(p.A748T)is a newly identified mutational site,which expands the genetic mutation map of INAD,and the whole exome sequencing data provide accurate genetic counseling and prenatal diagnosis for this family.

关 键 词：婴儿神经轴索营养不良 PLA2G6基因 全外显子测序 产前诊断 

分 类 号：R714.5[医药卫生—妇产科学] R440[医药卫生—临床医学]