摘要
目的探讨1例3M综合征(3MS)1型患儿的临床与遗传学特征。方法选取2021年2月于郑州大学附属儿童医院就诊的1例3MS 1型患儿为研究对象。采集患儿及其父母外周血样并提取基因组DNA, 对患儿进行全外显子组测序(WES), 对候选变异进行Sanger测序验证与致病性分析。以"3M综合征"与"3M syndrome"分别为中、英文关键词, 在中国知网、万方数据知识服务平台和PubMed数据库中检索相关文献, 检索时间为建库至2024年12月, 对已报道的中国3MS患儿相关临床资料进行总结。本研究已通过郑州大学附属儿童医院医学伦理委员会的审查(批准号:2024-K-020)。结果①患儿为6岁2月龄女性, 存在面部畸形、骨骼发育异常及生长发育迟缓。②WES检测显示患儿携带CUL7基因c.2686G>T(p.E896*)无义变异与c.1200delT(p.R401Gfs*66)移码变异;Sanger测序验证该2个变异分别遗传自患儿父亲和母亲;根据美国医学遗传学与基因组学学会(ACMG)制定的《遗传变异分类标准与指南》, c.2686G>T(p.E896*)被判定为致病性变异(PVS1+PM2Supporting+PM3), c.1200delT(p.R401Gfs*66)被判定为可能致病性变异(PVS1+PM2Supporting)。③根据本研究设定的文献检索策略, 共检索出18篇相关文献, 纳入共计32例中国3MS病例, 其中8例为胎儿;32例病例主要携带CUL7基因变异(20/32, 62.5%)与OBSL1基因变异(12/32, 37.5%);主要临床表现包括宫内或生后生长发育落后(32/32, 100.0%)、倒三角形面部特征(27/32, 84.3%)与骨骼发育异常(21/32, 65.6%)。结论 CUL7基因c.2686G>T(p.E896*)与c.1200delT(p.R401Gfs*66)复合杂合变异可能为上述3MS 1型患儿的遗传学病因。对于存在面部畸形、骨骼发育异常及宫内或产后生长发育落后等表现的患儿, 应警惕3MS可能。
Objective To explore the clinical features,genetic characteristics in a child with Miller-McKusick-Malvaux syndrome(3MS)type 1 caused by CUL7 gene variant.Methods A child diagnosed with 3MS type 1 at the Children's Hospital Affiliated to Zhengzhou University in February 2021 was selected as the subject of this study.Peripheral blood samples were collected from the child and her parents for genomic DNA extraction.Whole exome sequencing(WES)was performed on the child,and Sanger sequencing was used to validate the candidate variants and analyze their pathogenicity.A literature search was conducted using the keywords"3M syndrome"in the China National Knowledge Infrastructure,Wanfang Data Knowledge Service Platform,and PubMed databases from inception to December 2024.The clinical data of Chinese children with 3MS reported in the literature were summarized.This study was approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University(EthicsNo.2024-K-020).Resultss The child was a 6-year-old and 2-month-old female with facial dysmorphism,skeletal abnormalities,and growth and developmental delay.@WES revealed compound heterozygous variants in the CUL7 gene:c.2686G>T(p.E896*)and c.1200delT(p.R401Gfs66).Sanger sequencing confirmed that these two variants were inherited from the child's father and,mother,respectively.According to the American College of Medical Genetics and Genomics(ACMG)Standards and Guidelines for the Interpretation of Sequence Variants,c.2686G>T(p.E896)was classified as a pathogenic(PVS1+PM2_Supporting+PM3),and c.1200delT(p.R401Gfs*66)was classified as a likely pathogenic(PVS1+PM2_Supporting).③Based on the literature search strategy,18 relevant articles were identified,including a total of 32 Chinese cases of 3MS,of which 8 were fetuses.A total of 32 Chinese 3MS cases were included in the literature review,of which 8 were fetuses.The majority of these cases carried variants in the CUL7 gene(20/32,62.5%)and OBSL1 gene(12/32,37.5%).The main clinical manifestations included intrauterine or postnatal growth and developmental delay(32/32,100.0%),triangular facies(27/32,84.3%),and skeletal abnormalities(21/32,65.6%).Conclusion The compound heterozygous variants c.2686G>T(p.E896*)and c.1200delT(p.R401Gfs*66)in the CUL7 gene are likely the genetic cause of 3MS type 1 in the child.For children presenting with facial dysmorphism,skeletal abnormalities,and intrauterine or postnatal growth and developmental delay,3MS should be considered as a differential diagnosis.
作者
张利明
吴雪
杨建伟
孙红启
杨俊梅
陈永兴
Zhang Liming;Wu Xue;Yang Jianwei;Sun Hongqi;Yang Junmei;Chen Yongring(Department of Clinical Laboratory,Children's Hospital Affiliated to Zhengzhou University,Zhengzhou Key Laboratory of Children's Infection and Immunity,Zhengzhou,Henan 450018,China;Department of Endocrine Genetics and Metabolism,Children's Hospital Affiliated to Zhengzhou University,Zhengzhou,Henan 450018,China)
出处
《中华医学遗传学杂志》
2025年第3期343-348,共6页
Chinese Journal of Medical Genetics
基金
河南省医学科技攻关计划联合共建项目(LHGJ20240560)。
