2例胎儿15号小额外标记染色体产前遗传学分析
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摘要
目的:探讨染色体微阵列分析(CMA)诊断15q小额外标记染色体胎儿的临床价值。方法:获得2例高危孕妇的胎儿羊水或脐血细胞及其双亲外周血细胞,通过CMA和G显带染色体核型分析检测胎儿及其父母的染色体结构。结果:胎儿1:羊水细胞G显带核型分析结果为47,XX,+mar,CMA结果为arr15q11.2(22770421-23288350)×4,其父外周血细胞G显带核型分析结果为47,XY,+mar,母亲外周血染色体核型结果及CMA检测结果未见明显异常。胎儿2:脐血染色体G显带分析结果为47,XX,+mar,CMA结果为arr15q11.2q13.3(22770421-32439524)×4,其父母外周血染色体核型结果及CMA分析结果未见明显异常。结论:通过CMA检测和G显带核型分析结果显示,胎儿1存在15q11.2区域的四拷贝重复变异,经鉴定此携带小额外标记染色体为健康人群多态性。胎儿2存在15q11.2q13.3四拷贝重复小额外标记染色体,确诊为15q11.2q13.3微重复四倍体综合征,出生后可能引起较严重的异常表型。本文对两例15号染色体微重复胎儿进行了产前诊断,明确了胎儿基因型与表型的对应关系,为临床产前诊断和遗传咨询提供可靠的依据。
Objective: Prenatal diagnosis of 2 high-risk fetuses by using chromosome Microarray Analysis( Chromosomal Microarray Analysis,CMA).To explore the clinical value of CMA applicating in Supernumerary Marker Chromosome derivative chromosome 15 q.Methods:Fetal amniotic fluid or umbilical cord blood and their parents' peripheral blood wers collected.Used G banding and CMA to detect cells of two high risk fetal.Results: Fetus 1: The karyotype analysis results of fetal amniotic fluid was 47,XX,+ mar. The result of CMA was arr15 q11. 2( 2770421-23288350) x4.Its father's peripheral blood was 47,XY,+mar.Fetus 2: The karyotype analysis results of fetal umbilical cord blood was 47,XX,+ mar. The result of CMA was arr15 q11.2 q13.3( 22770421-32439524) x4.Conclusion: CMA test and G band karyotype analysis showed that there were four copies of repeated variation in 15 q11.2 region in fetal 1,which was identified as polymorphism in healthy population.Fetal 2 has 15 q11.2 q13.3 four copy duplication,and is diagnosed as 15 q11. 2 q13. 3 microduplication tetraploid syndrome,which may cause severe abnormal phenotype after birth.In this paper,prenatal diagnosis of two fetuses with microduplication on chromosome 15 was carried out,and the corresponding relationship between fetal genotype and phenotype was clarified,providing reliable basis for clinical prenatal diagnosis and genetic counseling.
Objective: Prenatal diagnosis of 2 high-risk fetuses by using chromosome Microarray Analysis( Chromosomal Microarray Analysis,CMA).To explore the clinical value of CMA applicating in Supernumerary Marker Chromosome derivative chromosome 15 q.Methods:Fetal amniotic fluid or umbilical cord blood and their parents' peripheral blood wers collected.Used G banding and CMA to detect cells of two high risk fetal.Results: Fetus 1: The karyotype analysis results of fetal amniotic fluid was 47,XX,+ mar. The result of CMA was arr15 q11. 2( 2770421-23288350) x4.Its father's peripheral blood was 47,XY,+mar.Fetus 2: The karyotype analysis results of fetal umbilical cord blood was 47,XX,+ mar. The result of CMA was arr15 q11.2 q13.3( 22770421-32439524) x4.Conclusion: CMA test and G band karyotype analysis showed that there were four copies of repeated variation in 15 q11.2 region in fetal 1,which was identified as polymorphism in healthy population.Fetal 2 has 15 q11.2 q13.3 four copy duplication,and is diagnosed as 15 q11. 2 q13. 3 microduplication tetraploid syndrome,which may cause severe abnormal phenotype after birth.In this paper,prenatal diagnosis of two fetuses with microduplication on chromosome 15 was carried out,and the corresponding relationship between fetal genotype and phenotype was clarified,providing reliable basis for clinical prenatal diagnosis and genetic counseling.
引文
[1]Christian SL,Fantes JA,Mewborn SK,et al.Large genomic duplicons map to sites of instability in the Prader-Willi/Angelman syndrome chromosome region(15q11-q13)[J].Hum Mol Genet,1999,8(6):1025-1037
[2]Makoff AJ,Flomen RH.Detailed analysis of 15q11-q14 sequence corrects errors and gaps in the public access sequence to fully reveal large segmental duplications at breakpoints for Prader-Willi,Angelman,and inv dup(15)syndromes[J].Genome Biol,2007,8(6):R114
[3]Donlon TA,Lalande M,Wyman A,et al.Isolation of molecular probes associated with the chromosome 15 instablity in the Prader-Willi syndrome[J].Proc Natl Acad Sci USA,1986,83(12):4408-4412
[4]Battaglia A.The inv dup(15)or idic(15)syndrome(Tetrasomy 15q)[J].Orphanet J Rare Dis,2008,3:30
[5]Lalande M.Parental imprinting and human disease[J].Ann Rev Genet,1996,30:173-195
[6]Browne CE,Dennis NR,Maher E,et al.Inherited interstitial duplications of proximal 15q:genotype-phenotype correlations[J].Am J Hum Genet,1997,61(6):1342-1352
[7]Crolla JA,Harvey JF,Sitch FL,et al.Supernumerary marker15 chromosomes:a clinical,molecular and FISH approach to diagnosis and prognosis[J].Hum Genet,1995,95(2):161-170
[8]Cheng SD,Spinner NB,Zackai EH,et al.Cytogenetic and molecular characterization of inverted duplicated chromosomes15 from 11 patients[J].Am J Hum Genet,1994,55(4):753-759
[9]涂向东,丛学文,曾健,等.四例男性不育患者的15q11额外小标记染色体分析[J].中华医学遗传学杂志,2013,30(5):539-543
[10]Hou JW,Wang TR.Unusual features in children with inv dup(15)supernumerary marker:a study of genotype-phenotype correlation in Taiwan[J].Eur J Pediatr,1998,157(2):122-127
[11]Robinson WP,Binkert F,Gine R,et al.Clinical and molecular analysis of five inv dup(15)patients[J].Eur J Hum Genet,1993,1(1):37-50
[12]Blennow E,Nielsen KB,Telenius H,et al.Fifty probands with extra structurally abnormal chromosomes characterized by fluorescence in situ hybridization[J].Am J Med Genet,1995,55(1):85-94
[13]Battaglia A,Gurrieri F,Bertini E,et al.The inv dup(15)syndrome:a clinically recognizable syndrome with altered behaviour,mental retardation and epilepsy[J].Neurology,1997,48(4):1081-1086
[14]Gillberg C,Steffenburg S,Wahlstrom J,et al.Autism associated with marker chromosome[J].J Am Acad Child Adolesc Psychiat,1991,30(3):489-494
[15]Battaglia A.The inv dup(15)or idic(15)syndrome:a clinically recognisable neurogenetic disorder[J].Brain Devel,2005,27(5):365-369
[16]South ST,Lee C,Lamb AN,et al.ACMG Standards and Guidelines for constitutional cytogenomic micriarray analysis,including postnatal and prenatal applications:revision2013[J].Genet Med,2013,15(11):901-909
[17]吴星,朱湘玉,张颖,等.85例生长受限胎儿染色体微阵列检测结果分析[J].中华围产医学杂志,2017,20(11):809-815
[18]廖灿.染色体微阵列分析技术在产前诊断中的应用[J].中华围产医学杂志,2014,17(12):804-808
[19]Urraca N1,Cleary J,Brewer V,et al.The interstitial duplication 15q11.2-q13 syndrome includes autism,mild facial anomalies and a characteristic EEG signature[J].Autism Res,2013,6(4):268-279
[20]Manvelyan M,Riegel M,Santos M,et al.Supernumerary marker chromosome 15 in a male with azoospermia and open bite deformity[J].Asian J Androl,2009,11(5):617-622
[21]钟福春,兰风华,张晓林,等.一例BP3:BP3重排inv dup(1 5)的临床表型和遗传学分析[J].中华医学遗传学杂,2017,34(3):402-405
[22]李小燕,陈倩,谢华,等.15q11.2-13.2微重复四倍体综合征1例并文献复习[J].中国循证儿科杂志,2015,10(4):292-296
[22]Dennis NR,Veltman MWM,Thompson R,et al.Clinical findings in 33 subjects with large supernumerary marker(15)chromosomes and 3 subjects with triplication of 15q11-q13[J].Am J Med Genet,2006,140(5):434-441
[2]Makoff AJ,Flomen RH.Detailed analysis of 15q11-q14 sequence corrects errors and gaps in the public access sequence to fully reveal large segmental duplications at breakpoints for Prader-Willi,Angelman,and inv dup(15)syndromes[J].Genome Biol,2007,8(6):R114
[3]Donlon TA,Lalande M,Wyman A,et al.Isolation of molecular probes associated with the chromosome 15 instablity in the Prader-Willi syndrome[J].Proc Natl Acad Sci USA,1986,83(12):4408-4412
[4]Battaglia A.The inv dup(15)or idic(15)syndrome(Tetrasomy 15q)[J].Orphanet J Rare Dis,2008,3:30
[5]Lalande M.Parental imprinting and human disease[J].Ann Rev Genet,1996,30:173-195
[6]Browne CE,Dennis NR,Maher E,et al.Inherited interstitial duplications of proximal 15q:genotype-phenotype correlations[J].Am J Hum Genet,1997,61(6):1342-1352
[7]Crolla JA,Harvey JF,Sitch FL,et al.Supernumerary marker15 chromosomes:a clinical,molecular and FISH approach to diagnosis and prognosis[J].Hum Genet,1995,95(2):161-170
[8]Cheng SD,Spinner NB,Zackai EH,et al.Cytogenetic and molecular characterization of inverted duplicated chromosomes15 from 11 patients[J].Am J Hum Genet,1994,55(4):753-759
[9]涂向东,丛学文,曾健,等.四例男性不育患者的15q11额外小标记染色体分析[J].中华医学遗传学杂志,2013,30(5):539-543
[10]Hou JW,Wang TR.Unusual features in children with inv dup(15)supernumerary marker:a study of genotype-phenotype correlation in Taiwan[J].Eur J Pediatr,1998,157(2):122-127
[11]Robinson WP,Binkert F,Gine R,et al.Clinical and molecular analysis of five inv dup(15)patients[J].Eur J Hum Genet,1993,1(1):37-50
[12]Blennow E,Nielsen KB,Telenius H,et al.Fifty probands with extra structurally abnormal chromosomes characterized by fluorescence in situ hybridization[J].Am J Med Genet,1995,55(1):85-94
[13]Battaglia A,Gurrieri F,Bertini E,et al.The inv dup(15)syndrome:a clinically recognizable syndrome with altered behaviour,mental retardation and epilepsy[J].Neurology,1997,48(4):1081-1086
[14]Gillberg C,Steffenburg S,Wahlstrom J,et al.Autism associated with marker chromosome[J].J Am Acad Child Adolesc Psychiat,1991,30(3):489-494
[15]Battaglia A.The inv dup(15)or idic(15)syndrome:a clinically recognisable neurogenetic disorder[J].Brain Devel,2005,27(5):365-369
[16]South ST,Lee C,Lamb AN,et al.ACMG Standards and Guidelines for constitutional cytogenomic micriarray analysis,including postnatal and prenatal applications:revision2013[J].Genet Med,2013,15(11):901-909
[17]吴星,朱湘玉,张颖,等.85例生长受限胎儿染色体微阵列检测结果分析[J].中华围产医学杂志,2017,20(11):809-815
[18]廖灿.染色体微阵列分析技术在产前诊断中的应用[J].中华围产医学杂志,2014,17(12):804-808
[19]Urraca N1,Cleary J,Brewer V,et al.The interstitial duplication 15q11.2-q13 syndrome includes autism,mild facial anomalies and a characteristic EEG signature[J].Autism Res,2013,6(4):268-279
[20]Manvelyan M,Riegel M,Santos M,et al.Supernumerary marker chromosome 15 in a male with azoospermia and open bite deformity[J].Asian J Androl,2009,11(5):617-622
[21]钟福春,兰风华,张晓林,等.一例BP3:BP3重排inv dup(1 5)的临床表型和遗传学分析[J].中华医学遗传学杂,2017,34(3):402-405
[22]李小燕,陈倩,谢华,等.15q11.2-13.2微重复四倍体综合征1例并文献复习[J].中国循证儿科杂志,2015,10(4):292-296
[22]Dennis NR,Veltman MWM,Thompson R,et al.Clinical findings in 33 subjects with large supernumerary marker(15)chromosomes and 3 subjects with triplication of 15q11-q13[J].Am J Med Genet,2006,140(5):434-441
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