全基因组SNP-array在新生儿畸形遗传学诊断中的价值评估
摘要
目的评价全基因组SNP-array在新生儿畸形遗传学诊断中的价值。方法收集2013年7月-2017年7月嘉兴市妇幼保健院及安庆市第一人民医院新生儿科发现有畸形的450例新生儿的外周血,使用SNP-array对外周血的全基因组DNA拷贝数变异(CNV)进行检测,然后采用Affymetrix 750K芯片分析样本情况,并进行核型检查,验证芯片异常结果。结果 450例样本中,行SNP-array检测均获得成功,检测成功率为100. 00%。各系统异常CNV检出率的比较中,中枢神经系统、胎儿水肿综合征、羊水过多、淋巴水囊瘤、心血管异常CNV检出率最高,其次为颜面部异常、肌肉骨骼系统、NT增厚和多发畸形,消化系统异常、软指标异常、胎儿肿瘤的检出率最低,均未出现变异。经核型检测可得,三倍体、非整倍体共36例,异常检出率为8. 00%。除了良性CNV,具有临床意义的变异经高分辨率染色体微阵列分析(CMA)检出86例,异常检出率为19. 11%。36例为染色体数目异常,异常检出率为8. 00%,包括6例三倍体和30例非整倍体,符合核型结果;通过正常核型检测,芯片提示存在CNV的有58例(12. 89%),其中临床意义明确的致病性CNV有44例,异常检出率为9. 78%,临床意义暂未明确的有14例,异常检出率为3. 11%。结论全基因组SNP-array技术对新生儿畸形遗传学诊断具有准确性好、分辨率高等特点,引入SNP-array平台进行产前诊断对发现更多未知的综合征型疾病具有积极的意义,为临床遗传病咨询和诊断提供依据,值得在临床推广应用。
引文
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[22]Audrézet MP,Munck A,Scotet V,et al.Comprehensive CFTRgene analysis of the French cystic fibrosis screened newborn cohort:implications for diagnosis,genetic counseling,and mutation-specific therapy[J].Genet Med,2015,17(2):108-116.
[23]姜湖铃,平泽朋,王路明,等.应用BACs-on-BeadsTM和SNP-array技术产前诊断18p四体综合征一例[J].中华医学遗传学杂志,2017,34(6):857-860.
[24]Chu CW,Chen YJ,Lee YH,et al.Government-funded universal newborn hearing screening and genetic analyses of deafness predisposing genes in Taiwan[J].Int J Pediatr Otorhinolaryngol,2015,79(4):584-590.
[25]李素萍,沈华祥,金玉霞,等.应用单核苷酸多态性-微阵列技术产前诊断胎儿标记染色体确诊Pallister-Killian综合征一例[J].中华医学遗传学杂志,2016,33(5):682-685.
[2]Lisi EC,Mccandless SE.Newborn screening for lysosomal storage disorders:views of genetic healthcare providers[J].J Genet Couns,2016,25(2):373-384.
[3]林少宾,罗艳敏,吴坚柱,等.两例Miller-Dieker综合征胎儿的产前遗传学分析[J].中华医学遗传学杂志,2017,34(1):89-92.
[4]Genetics CO.Committee opinion no.616:Newborn screening and the role of the obstetrician-gynecologist[J].Obstet Gynecol,2015,125(1):256-260.
[5]王环环,肖冰,叶荟,等.一例发育落后合并多发畸形的16p13.11微缺失综合征患儿的临床及遗传学分析[J].中华医学遗传学杂志,2016,33(4):485-489.
[6]林少宾,张志强,吴坚柱,等.一例1q部分单体并17q部分三体胎儿的遗传学分析[J].中华医学遗传学杂志,2016,33(3):340-343.
[7]Pasquali M,Longo N.Newborn screening and inborn errors of metabolism[J].Am J Med Genet C Semin Med Genet,2015,157(1):1-2.
[8]Gelb MH,Scott CR,Turecek F,et al.Comparison of tandem mass spectrometry to fluorimetry for newborn screening of LSDs[J].Mol Genet Metab Rep,2017,12(C):80-81.
[9]吴轲,唐少华,陈冲,等.产前超声异常胎儿的全基因组拷贝数变异分析[J].中华医学遗传学杂志,2017,34(2):178-182.
[10]Shin SY,Yoo HW,Lee BH,et al.Identification of the mechanism underlying a human chimera by SNP array analysis[J].Am J Med Genet A,2016,158A(9):2119-2123.
[11]王环环,唐利芳,张静敏,等.一例Tietz综合征(或)Waardenburg TypeⅡA综合征患者的临床表型与遗传学分析[J].中华医学遗传学杂志,2015,32(4):520-523.
[12]Yahya VMM,Masoud DT,Mahmoud NS,et al.Newborn with supernumerary marker chromosome derived from chromosomes 11 And22-a case report[J].Iran J Public Health,2016,45(3):376-380.
[13]Knopp C,Rudnik-Sch9neborn S,Eggermann T,et al.Syndromic ciliopathies:From single gene to multi gene analysis by SNP arrays and next generation sequencing[J].Mol Cell Probes,2015,29(5):299-307.
[14]Stark Z,Behrsin J,Burgess T,et al.SNP microarray abnormalities in a cohort of 28 infants with congenital diaphragmatic hernia[J].Am J Med Genet A,2015,167(10):2319-2326.
[15]Ottolini CS,Newnham LJ,Capalbo A,et al.Genome-wide maps of recombination and chromosome segregation in human oocytes and embryos show selection for maternal recombination rates.[J].Nat Genet,2015,47(7):727-735.
[16]沈学萍,何平亚,方嵘,等.一例Wolf-Hirschhorn综合征合并Edward综合征胎儿的遗传学分析[J].中华医学遗传学杂志,2017,34(5):714-717.
[17]刘静,席惠,王华,等.SNP array在胎儿超声异常及孕妇不良生育史产前诊断中的应用研究[J].中华医学遗传学杂志,2017,34(2):173-177.
[18]史珊珊,潘观玉,杨艳东,等.应用SNP array诊断一例5p缺失综合征合并11q部分三体胎儿[J].中华医学遗传学杂志,2016,33(2):195-199.
[19]金玉霞,刘霞,李素萍,等.单核苷酸多态微阵列技术确诊Wolf-Hirschhorn综合征一例[J].中华医学遗传学杂志,2016,33(4):501-504.
[20]Regier DS,Ferreira C,Hart S,et al.Medical genetics and genomic medicine in the United States.Part 2:reproductive genetics,newborn screening,genetic counseling,training,and registries[J].Mol Genet Genomic Med,2017,5(6):621-630.
[21]史珊珊,林少宾,廖燕芬,等.SNP array精确诊断1型缺失型Angelman综合征一例[J].中华医学遗传学杂志,2016,33(6):824-828.
[22]Audrézet MP,Munck A,Scotet V,et al.Comprehensive CFTRgene analysis of the French cystic fibrosis screened newborn cohort:implications for diagnosis,genetic counseling,and mutation-specific therapy[J].Genet Med,2015,17(2):108-116.
[23]姜湖铃,平泽朋,王路明,等.应用BACs-on-BeadsTM和SNP-array技术产前诊断18p四体综合征一例[J].中华医学遗传学杂志,2017,34(6):857-860.
[24]Chu CW,Chen YJ,Lee YH,et al.Government-funded universal newborn hearing screening and genetic analyses of deafness predisposing genes in Taiwan[J].Int J Pediatr Otorhinolaryngol,2015,79(4):584-590.
[25]李素萍,沈华祥,金玉霞,等.应用单核苷酸多态性-微阵列技术产前诊断胎儿标记染色体确诊Pallister-Killian综合征一例[J].中华医学遗传学杂志,2016,33(5):682-685.