淋巴水肿-双行睫综合征2个家系的临床特征及遗传学分析  

Clinical features and genetic analysis of two Chinese pedigrees affected with Lymphedema-Distichiasis syndrome

作　　者：李静[1] 袁莉敏[1] 翟闪闪[1] 李乃琪 王涵铎 韩笑[1] 赵岚岚[1] 李娟 崔世红[1] 刘灵[1] Li Jing;Yuan Limin;Zhai Shanshan;Li Naiqi;Wang Handuo;Han Xiao;Zhao Lanlan;Li Juan;Cui Shihong;Liu Ling(Medical Genetics and Prenatal Diagnosis Department,the Third Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第三附属医院医学遗传与产前诊断科,郑州450052

出　　处：《中华医学遗传学杂志》2024年第12期1441-1447,共7页Chinese Journal of Medical Genetics

基　　金：河南省重点研发与推广专项(科技攻关)(212102310471)。

摘　　要：目的探究FOXC2基因变异所致淋巴水肿-双行睫综合征(LDS)患者的临床特征及遗传学特点。方法回顾性分析郑州大学第三附属医院接诊的2个LDS家系的表型信息、胎儿超声影像资料以及遗传学检测结果,并以"淋巴水肿-双行睫综合征""Lymphedema-Distichiasis syndrome""FOXC2"为关键词,对中国知网、万方数据库和PubMed数据库2010年1月至2024年6月收录的文献进行检索,总结FOXC2基因变异所致的LDS病例的表型及基因型特点。本研究通过了郑州大学第三附属医院医学伦理委员会的审查(批准号:2021-046-01)。结果2个家系均未检测到染色体非整倍体或100 kb以上的致病性拷贝数变异。家系1胎儿检测到FOXC2基因c.361C>T(p.R121C)杂合变异,家系2胎儿检测到FOXC2基因c.168C>A(p.Y56*)杂合变异,二者均为父源性,根据ACMG相关指南分别评级为致病性和可能致病性。文献回顾共收集到20篇文献,结合本研究的家系共117例患者,其中13例具有产前表型,主要包括NT增厚(12/13)、泌尿系统异常(5/12)和胎儿水肿(4/13),110例具有产后表型,主要包括双行睫(87/110)和淋巴水肿(73/110)。共发现32种基因变异。结论LDS的主要产前表现包括NT增厚、胎儿水肿、胸腹腔积液、双肾集合系统分离,产后表型主要为淋巴水肿、双行睫以及脊髓硬膜外蛛网膜囊肿。FOXC2基因的c.168C>A变异扩展了我国FOXC2基因的变异谱。ObjectiveTo explore the prenatal and postnatal features and genetic characteristics of patients with Lymphedema-Distichiasis syndrome(LDS)due to variants of FOXC2 gene.MethodsA retrospective analysis was carried out on the phenotypic information,fetal ultrasound image,and genetic testing of two Chinese pedigrees diagnosed at the Third Affiliated Hospital of Zhengzhou University.A literature review was also carried out by searching the China National Knowledge Infrastructure(CNKI),Wanfang Database,and PubMed databases dated from January 2010 to June 2024 using keywords"Lymphedema-Distichiasis syndrome"and"FOXC2".This study has been approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University(Ethic No.2021-046-01).ResultsNeither family was found to harbor chromosomal aneuploidy or pathogenic CNVs larger than 100 kb.The fetuses from pedigree 1 and pedigree 2 were respectively found to be heterozygous for a c.361C>T(p.R121C)variant and a c.168C>A(p.Y56*)variant of the FOXC2 gene.Both variants were paternally derived.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the variants were classified as pathogenic and likely pathogenic,respectively.Literature search has identified 20 articles,and combined with our cases,a total of 117 patients were identified.Among them,13 had shown prenatal phenotypes,primarily with increased nuchal translucency(NT)(12/13),urinary abnormalities(5/12),and fetal edema(4/13).Postnatal phenotypes were observed in 110 cases,mainly as distichiasis(87/110)and lymphedema(73/110).Only 6 cases had both prenatal and postnatal phenotypes.A total of 32 genetic variants were identified.ConclusionThe primary prenatal manifestations of LDS include increased NT,fetal edema,pleural and abdominal effusion,and separation of renal collecting system.Postnatal phenotypes are primarily characterized by lymphedema,distichiasis,and spinal extradural arachnoid cysts.Discovery of the c.168C>A variant has expanded the spectrum of FOXC2 gene mu

关 键 词：淋巴水肿-双行睫综合征 胎儿期 FOXC2基因 产前诊断 遗传咨询 

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