胎儿侧脑室增宽的遗传学研究进展

赵晨玥; 张莉雪; 蒋劲嵩; 郭敏; 高景波; 郭荣; 曹桂芝; 薛慧琴

doi:10.11852/zgetbjzz2024-0019

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中国儿童保健杂志 ›› 2024, Vol. 32 ›› Issue (12) : 1322-1327. DOI: 10.11852/zgetbjzz2024-0019

综述

胎儿侧脑室增宽的遗传学研究进展

赵晨玥¹, 张莉雪¹, 蒋劲嵩¹, 郭敏¹, 高景波², 郭荣², 曹桂芝², 薛慧琴²

作者信息 +

Genetic advances in the fetal ventriculomegaly

ZHAO Chenyue¹, ZHANG Lixue¹, JIANG Jinsong¹, GUO Min¹, GAO Jingbo², GUO Rong², CAO Guizhi², XUE Huiqin²

Author information +

文章历史 +

摘要

侧脑室增宽(VM) 是一种产前检查中常见的胎儿超声异常表现,发生率约为1%,与儿童智力和精神运动的发展密切相关,通过产前超声或MRI检查可以评估侧脑室的大小和形态。引起侧脑室增宽的原因有中枢神经系统发育畸形、染色体畸变、基因突变、遗传综合征和其它一些未知疾因等,其中遗传学病因占有很大比重,并且已经成为了许多家庭关注的问题。本综述将回顾和总结胎儿VM的遗传学研究进展,包括遗传学病因及其相关的分子机制,以及遗传病因的诊断与鉴定。

Abstract

Ventriculomegaly (VM) is a common fetal ultrasound abnormality in prenatal screening,with an incidence of about 1%,and is closely related to the intellectual and psychomotor development of children,which can be evaluated by prenatal ultrasound or MRI that can assess its size and morphology.VM can be caused by central nervous system malformations,chromosomal aberrations,gene mutations,genetic syndromes and potential fetal anomalies,with genetics etiology accounting for a large portion of the cases and has become a concern for many families.This review combs genetic advances in fetal VM,including the genetics etiology and its associated molecular mechanisms,as well as the diagnosis and identification of genetic etiologies.

导出引用

赵晨玥, 张莉雪, 蒋劲嵩, 郭敏, 高景波, 郭荣, 曹桂芝, 薛慧琴. 胎儿侧脑室增宽的遗传学研究进展[J]. 中国儿童保健杂志. 2024, 32(12): 1322-1327 https://doi.org/10.11852/zgetbjzz2024-0019

ZHAO Chenyue, ZHANG Lixue, JIANG Jinsong, GUO Min, GAO Jingbo, GUO Rong, CAO Guizhi, XUE Huiqin. Genetic advances in the fetal ventriculomegaly[J]. Chinese Journal of Child Health Care. 2024, 32(12): 1322-1327 https://doi.org/10.11852/zgetbjzz2024-0019

中图分类号： R714.5

参考文献

[1] Society for Maternal-Fetal M,Norton ME,Fox NS,et al.Fetalventriculomegaly[J].Am J Obstet Gynecol,2020,223(6):B30-B33.
[2] Mirsky DM,Stence NV,Powers AM,et al.Imaging of fetal ventriculomegaly[J].Pediatr Radiol,2020,50(13):1948-1958.
[3] Pisapia JM,Sinha S,Zarnow DM,et al.Fetal ventriculomegaly: Diagnosis,treatment,and future directions[J].Childs Nerv Syst,2017,33(7):1113-1123.
[4] Ryan GA,Start AO,Cathcart B,et al.Prenatal findings and associated survival rates in fetal ventriculomegaly: A prospective observational study[J].Int J Gynaecol Obstet,2022,159(3):891-897.
[5] 孙燕,张为远.胎儿侧脑室增宽与预后的荟萃分析[J].中华妇产科杂志,2018,53(10):677-682.
Sun Y,Zhang WY.Meta analysis of fetal lateral ventriculomegaly and prognosis[J].Chin J Obstet Gynecol,2018,53(10):677-682.(in Chinese)
[6] 黄晓莉,孙丽洲.218例侧脑室增宽胎儿的染色体检测结果和妊娠结局分析[J].南京医科大学学报(自然科学版),2021,41(4):593-599,633.
Huang XL,Sun LZ.Analysis of chromosome detection and pregnancy outcome in 218 cases of fetuses with lateral ventricle widening[J].J Nanjing Med Univ(Natural Sciences),2021,41(4):593-599,633.(in Chinese)
[7] Duan HL,Zhu XY,Zhu YJ,et al.The application of chromosomal microarray analysis to the prenatal diagnosis of isolated mild ventriculomegaly[J].Taiwan J Obstet Gynecol,2019,58(2):251-254.
[8] Santirocco M,Plaja A,Rodo C,et al.Chromosomal microarray analysis in fetuses with central nervous systemanomalies: An 8-year long observational study from a tertiary care university hospital[J].Prenat Diagn,2021,41(1): 123-135.
[9] Gezer C,Ekin A,Ozeren M,et al.Chromosome abnormality incidence in fetuses with cerebral ventriculomegaly[J].J Obstet Gynaecol,2014,34(5):387-391.
[10] 何敏,胡莎,胡婷,等.胎儿临界性侧脑室增宽与染色体异常的相关性[J].中华妇产科杂志,2018,53(10):660-664.
He M,Hu S,Hu T,et al.Correlation between fetal borderline ventriculomegaly and chromosomal abnormalities[J].Chin J Obstet Gynecol,2018,53(10):660-664.(in Chinese)
[11] 王恒,时盼来,王建红,等.CNV-seq 在侧脑室增宽胎儿产前诊断中的应用价值[J].中华医学遗传学杂志,2021,38(3):293-295.
Wang H,Shi PL,Wang JH,et al.Application value of CNV-seq in prenatal diagnosis of ventriculomegaly fetus[J].Chin J Med Genet,2021,38(3):293-295.(in Chinese)
[12] 周晖登,曾尚娟,唐文庭.广西地区425例侧脑室增宽胎儿遗传学因素分析[J].中国优生与遗传杂志,2019,27(6):749-751.
Zhou HD,Zeng SJ,Tang WT.Genetic testing and pregnant outcomes of 425 cases ventriculomegaly fetuses[J].Chin J Birth Health Heredity,2019,27(6):749-751.(in Chinese)
[13] Hiramoto T,Sumiyoshi A,Yamauchi T,et al.Tbx1,a gene encoded in 22q11.2 copy number variant,is a link between alterations in fimbria myelination and cognitive speed in mice[J].Mol Psychiatry,2022,27(2):929-938.
[14] Merico D,Costain G,Butcher NJ,et al.MicroRNA dysregulation,gene networks,and risk for schizophrenia in 22q11.2 deletion syndrome[J].Front Neurol,2014(5):238.
[15] Zinkstok JR,Boot E,Bassett AS,et al.Neurobiological perspective of 22q11.2 deletion syndrome[J].The Lancet Psychiatry,2019,6(11):951-960.
[16] Rasmussen M,Vestergaard EM,Graakjaer J,et al.17q12 deletion and duplication syndrome in Denmark-a clinical cohort of 38 patients and review of the literature[J].Am J Med Genet A,2016,170A(11):2934-2942.
[17] Warren EB,Briano JA,Ellegood J,et al.17q12 deletion syndrome mouse model shows defects in craniofacial,brain and kidney development,and glucose homeostasis[J].Dis Model Mech,2022,15(12):dmm049752.
[18] Nittel CM,Dobelke F,Konig J,et al.Review of neurodevelopmental disorders in patients with HNF1B gene variations[J].Front Pediatr,2023(11):1149875.
[19] Cai M,Lin M,Guo N,et al.Prenatal ultrasound phenotypic and genetic etiology of the 17q12 microduplication syndrome[J].Front Pediatr,2022(10):910497.
[20] Vasileiou G,Hoyer J,Thiel CT,et al.Prenatal diagnosis of HNF1B-associated renal cysts: Is there a need to differentiate intragenic variants from 17q12 microdeletion syndrome?[J].Prenat Diagn,2019,39(12):1136-1147.
[21] Lok WY,Kong CW,Hui SYA,et al.Chromosomal abnormalities and neurological outcomes in fetal cerebral ventriculomegaly: A retrospective cohort analysis[J].Hong Kong Med J,2021,27(6):428-436.
[22] Kousi M,Katsanis N.The Genetic basis of hydrocephalus[J].Annu Rev Neurosci,2016(39):409-435.
[23] McKnight I,Hart C,Park IH,et al.Genes causing congenital hydrocephalus: Their chromosomal characteristics of telomere proximity and DNA compositions[J].Exp Neurol,2021,335:113523.
[24] Patzke C,Acuna C,Giam LR,et al.Conditional deletion of L1CAM in human neurons impairs both axonal and dendritic arborization and action potential generation[J].J Exp Med,2016,213(4):499-515.
[25] Stumpel C,Vos YJ.L1 Syndrome[M/OL].2004-04/28 [Updated 2021 Jan 7].Adam MP,Feldman J,Mirzaa GM,et al.GeneReviews^®[Internet].Seattle(WA): University of Washington,Seattle,1993-2023.
[26] Marivin A,Garcia-Marcos M.DAPLE and MPDZ bind to each other and cooperate to promote apical cell constriction[J].Mol Biol Cell,2019,30(16):1900-1910.
[27] Feldner A,Adam MG,Tetzlaff F,et al.Loss of Mpdz impairs ependymal cell integrity leading to perinatal-onset hydrocephalus in mice[J].EMBO Mol Med,2017,9(7):890-905.
[28] Su N,Jin M,Chen L.Role of FGF/FGFR signaling in skeletal development and homeostasis: Learning frommouse models[J].Bone Res,2014(2):14003.
[29] Coll G,El Ouadih Y,Abed Rabbo F,et al.Hydrocephalus and Chiari malformation pathophysiology in FGFR2-related faciocraniosynostosis: A review[J].Neurochirurgie,2019,65(5):264-268.
[30] Hebron KE,Hernandez ER,Yohe ME.The RASopathies: From pathogenetics to therapeutics[J].Dis Model Mech,2022,15(2):dmm049107.
[31] Scott A,Di Giosaffatte N,Pinna V,et al.When to test fetuses for RASopathies? Proposition from a systematic analysis of 352 multicenter cases and a postnatal cohort[J].Genet Med,2021,23(6):1116-1124.
[32] Zenker M.Clinical overview on RASopathies[J].Am J Med Genet C Semin Med Genet,2022,190(4):414-424.
[33] Basten SG,Giles RH.Functional aspects of primary cilia in signaling,cell cycle and tumorigenesis[J].Cilia,2013,2(1):6.
[34] Andreu-Cervera A,Catala M,Schneider-Maunoury S.Cilia,ciliopathies and hedgehog-related forebrain developmental disorders[J].Neurobiol Dis,2021(150):105236.
[35] Society for Maternal-Fetal M,Monteagudo A.Dandy-Walker malformation[J].Am J Obstet Gynecol,2020,223(6):B38-B41.
[36] Kumar V,Umair Z,Kumar S,et al.The regulatory roles of motile cilia in CSF circulation and hydrocephalus[J].Fluids Barriers CNS,2021,18(1):31.
[37] Duy PQ,Greenberg ABW,Butler WE,et al.Rethinking the cilia hypothesis of hydrocephalus[J].Neurobiol Dis,2022(175):105913.
[38] Mirzaa G.MPPH syndrome[M].University of Washington,1993-2024.
[39] Riviere JB,Mirzaa GM,O'Roak BJ,et al.De novo germline and postzygotic mutations in AKT3,PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes[J].Nat Genet,2012,44(8):934-940.
[40] Shi X,Lim Y,Myers AK,et al.PIK3R2/Pik3r2 activating mutations result in brain overgrowth and EEG changes[J].Ann Neurol,2020,88(6):1077-1094.
[41] Mirzaa GM,Conti V,Timms AE,et al.Characterisation of mutations of the phosphoinositide-3-kinase regulatory subunit,PIK3R2,in perisylvian polymicrogyria: A next-generation sequencing study[J].Lancet Neurol,2015,14(12):1182-1195.
[42] Alcantara D,Timms AE,Gripp K,et al.Mutations of AKT3 are associated with a wide spectrum of developmental disorders including extreme megalencephaly[J].Brain,2017,140(10):2610-2622.
[43] Bigger BW,Begley DJ,Virgintino D,et al.Anatomical changes and pathophysiology of the brain in mucopolysaccharidosis disorders[J].Mol Genet Metab,2018,125(4):322-331.
[44] Jovanovic M,Guterman-Ram G,Marini JC.Osteogenesis imperfecta: Mechanisms and signaling pathways connecting classical and rare OI types[J].Endocr Rev,2022,43(1):61-90.
[45] Bodensteiner JB.Neurologicalmanifestations of achondroplasia[J].Curr Neurol Neurosci Rep,2019,19(12):105.
[46] Brancaccio A.A molecular overview of the primary dystroglycanopathies[J].J Cell Mol Med,2019,23(5):3058-3062.
[47] Ge L,Zhang C,Wang Z,et al.Congenital muscular dystrophies in China[J].Clin Genet,2019,96(3):207-215.
[48] Mizuguchi M,Ohsawa M,Kashii H,et al.Brain symptoms of tuberous sclerosis complex: Pathogenesis and treatment[J].Int J Mol Sci,2021,22(13):6677.
[49] Lu DS,Karas PJ,Krueger DA,et al.Central nervous system manifestations of tuberous sclerosis complex[J].Am J Med Genet C Semin Med Genet,2018,178(3):291-298.
[50] Society for Maternal-Fetal M,Dugoff L,Norton ME,et al.The use of chromosomal microarray for prenatal diagnosis[J].Am J Obstet Gynecol,2016,215(4):B2-B9.
[51] Manickam K,McClain MR,Demmer LA,et al.Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: An evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG)[J].Genet Med,2021,23(11):2029-2037.
[52] 中国预防医学会出生缺陷预防与控制专业委员会产前筛查和诊断学组,中华医学会医学遗传学分会产前诊断学组.染色体微阵列分析技术在产前诊断中的应用指南(2023)[J].中华妇产科杂志,2023,58(8):565-575.
Prenatal Screening and Diagnosis Group,Birth Defect Prevention and Control Professional Committee.Guideline for the application of chromosomal microarray analysis in prenatal diagnosis (2023)[J].Chin J Obstet Gynecol,2023,58(8):565-575.(in Chinese)
[53] Shaheen R,Sebai MA,Patel N,et al.The genetic landscape of familial congenital hydrocephalus[J].Ann Neurol,2017,81(6):890-897.
[54] Giorgione V,Haratz KK,Constantini S,et al.Fetal cerebral ventriculomegaly: What do we tell the prospective parents?[J].Prenat Diagn,2022,42(13):1674-1681.
[55] Baptiste C,Mellis R,Aggarwal V,et al.Fetal central nervous system anomalies: When should we offer exome sequencing?[J].Prenat Diagn,2022,42(6):736-743.
[56] Wright CF,FitzPatrick DR,Firth HV.Paediatric genomics: diagnosing rare disease in children[J].Nat Rev Genet,2018,19(5):253-268.

基金

国家人口与生殖健康科学数据中心工程项目(No2005DKA32408);山西省回国留学人员科研教研资助项目(2023-180);山西省“2021年度“四个一批”科技兴医创新计划项目”医学遗传学研究委级重点实验室建设项目(2021SYS24);山西省儿童医院博士基金项目(201948);山西省卫生健康委员会资助项目(2023016)