摘要
目的探讨1个CNGA3基因变异所致的全色盲(ACHM)家系的遗传学特征,为其遗传咨询和生育指导提供依据。方法选取2023年4月14日于宁波大学附属妇女儿童医院就诊的1个ACHM家系为研究对象。应用全外显子组测序(WES)对先证者进行检测,对候选变异进行Sanger测序家系验证与生物信息学分析。在数据库中检索相关文献,总结CNGA3基因变异所致中国ACHM患者的临床表型与基因型特点。本研究通过宁波大学附属妇女儿童医院医学伦理委员会的审查(伦理号:EC2020-048)。结果WES检测结果显示先证者及其弟弟CNGA3基因第8外显子均存在c.1190G>T(p.Gly397Val)和c.2013del(p.Gly672ValfsTer69)复合杂合变异,分别遗传自其母亲和父亲。c.1190G>T为已知的致病性变异,c.2013del既往未见报道。根据美国医学遗传学与基因组学学会(ACMG)相关指南,c.2013del被判定为可能致病性变异(PM2_Supporting+PVS1_Moderate+PM3+PP4)。文献共检索出中国38个家系43例CNGA3基因变异相关的ACHM患者(包含上述先证者),共发现41种CNGA3基因变异,其中以错义变异为主,多数变异位于第8外显子;男性居多,以婴儿期/儿童期出现眼球震颤、畏光、弱视等症状为主要临床表现,未见明显的基因型-表型的对应关系。结论CNGA3基因c.1190G>T和c.2013del复合杂合变异可能是上述先证者的遗传学病因。c.2013del变异的检出丰富了中国人群CNGA3基因的变异谱,为临床诊断ACHM提供了依据。
ObjectiveTo explore the molecular basis for a Chinese pedigree affected with Achromatopsia(ACHM).MethodsA pedigree with ACHM which was admitted to the Women and Children′s Hospital of Ningbo University on April 14,2023 was selected as the study subject.Whole exome sequencing(WES)was carried out for the proband.Candidate variants were verified by Sanger sequencing and bioinformatic analysis.Related literature was reviewed,and clinical and genetic features of Chinese patients with ACHM due to variants of CNGA3 gene were summarized.This study was approved by the Women and Children′s Hospital of Ningbo University(Ethics No.EC2020-048).ResultsWES revealed that the proband and his younger brother had both harbored compound heterozygous variants of the CNGA3 gene,namely c.1190G>T(p.Gly397Val)and c.2013del(p.Gly672ValfsTer69),which were respectively inherited from their mother and father.The c.1190G>T was a known pathogenic variant,while the c.2013del was unreported previously.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the c.2013del variant was predicted to be likely pathogenic(PM2_Supporting+PVS1_Moderate+PM3+PP4).Literature review has identified 41 CNGA3 gene variants among 43 patients from 38 pedigrees,most of which were missense variants and had located in exon 8.Most patients were males,with nystagmus,photophobia,amblyopia and other symptoms during infancy/childhood as the main clinical manifestations,and there was a lack of genotype-phenotype correlation.ConclusionThe c.1190G>T(p.Gly397Val)and c.2013del(p.Gly672ValfsTer69)variants of the CNGA3 gene probably underlay the ACHM in the proband.Discovery of the c.2013del variant has enriched the mutational spectrum of the CNGA3 gene and provided a basis for genetic counseling and reproduction guidance for this pedigree.
作者
刘颖文
张玉鑫
闫露露
解敏
李海波
Liu Yingwen;Zhang Yuxin;Yan Lulu;Xie Min;Li Haibo(Department of Integrated Birth Defect Control,Women and Children′s Hospital of Ningbo University,Ningbo,Zhejiang 315012,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2024年第9期1077-1083,共7页
Chinese Journal of Medical Genetics
基金
宁波市医疗卫生高端团队(2022020405)
宁波市重点技术研发项目(2023Z178)
宁波市社会公益项目(2022S035)。
