CNV-Seq技术在先天异常胎儿遗传学检测的应用价值研究
|
摘要
目的本研究针对先天发育异常胎儿,联合应用染色体G显带核型分析技术与CNV-Seq技术,探讨发育异常胎儿中染色体异常的发生情况;并探讨CNV-Seq技术在检测染色体异常中的应用价值。方法对发育异常胎儿的羊水或脐带血进行染色体核型分析及CNV-Seq检测,探讨CNV-Seq技术在染色体异常检测中的应用价值。结果结合CNV-Seq技术,额外检出致病性拷贝数变异者4例(40.00%,4/10),结论胎儿发育异常与染色体核型异常有密切关系,染色体G显带核型分析联合CNV-Seq技术是一种快速、经济、有效的检测发育异常胎儿染色体异常的方法。
Objective:Birth defect refers to the anatomic and functional abnormalities in the development of the embryo or fetus,which can be caused by genetic factors,environmental factors and so on. In order to understand the relationship between fetal dysplasia and chromosomal abnormality,this study used chromosome G-banding karyotype analysis technique and CNVSeq technique to explore the occurrence of chromosomal abnormalities with congenital dysplasia. Method:Collected fetal data in Shenyang women and children Hospital from January 1,2018 to July 31,2018,chromosome karyotype analysis and CNV-Seq analysis were used to analyze 103 cases of congenital dysplasia.The abnormal rate of fetal chromosome was counted and the application value of CNV-Seq technique in detecting chromosome abnormality was discussed. Result:The incidence of chromosomal abnormality was 9.71%(10/103)in the dysplastic fetus. Only 6 cases(60.00%,6/10)was detected by karyotype analysis technique,including 1 case of trisomy 13,trisomy 18,2 cases of trisomy 21,triploid and 1 case of chromosome structure abnormals. Combined with CNV-Seq technique,4 cases of pathogenicity copy number variations were detected.(40.00%,4/10)Conclusion:The chromosomal G-banding karyotype combined with CNV-Seq technique is a rapid,economical and effective method for the detection of fetal chromosomal abnormalities.
Objective:Birth defect refers to the anatomic and functional abnormalities in the development of the embryo or fetus,which can be caused by genetic factors,environmental factors and so on. In order to understand the relationship between fetal dysplasia and chromosomal abnormality,this study used chromosome G-banding karyotype analysis technique and CNVSeq technique to explore the occurrence of chromosomal abnormalities with congenital dysplasia. Method:Collected fetal data in Shenyang women and children Hospital from January 1,2018 to July 31,2018,chromosome karyotype analysis and CNV-Seq analysis were used to analyze 103 cases of congenital dysplasia.The abnormal rate of fetal chromosome was counted and the application value of CNV-Seq technique in detecting chromosome abnormality was discussed. Result:The incidence of chromosomal abnormality was 9.71%(10/103)in the dysplastic fetus. Only 6 cases(60.00%,6/10)was detected by karyotype analysis technique,including 1 case of trisomy 13,trisomy 18,2 cases of trisomy 21,triploid and 1 case of chromosome structure abnormals. Combined with CNV-Seq technique,4 cases of pathogenicity copy number variations were detected.(40.00%,4/10)Conclusion:The chromosomal G-banding karyotype combined with CNV-Seq technique is a rapid,economical and effective method for the detection of fetal chromosomal abnormalities.
引文
[1]Schaaf CP,Wiszniewska J,Beaudet AL. Copy number and SNP arrays in clinical diagnostics[J]. Annu Rev Genomics Hum Genet,2011,12:25-51.
[2]Callaway JL,Shaffer LG,Chitty LS,et al. The clinical utility of microarray technologies applied to prenatal cytoge-netics in the presence of a normal conventional karyotype:a review of the literature[J]. Prenat Diagn,2013,33:1119e1123.
[3]Schwartz S. Clinical utility of single nucleotide polymorphism arrays[J]. Clin Lab Med,2011,31:581-594.
[4]Bian XM,Guo Q,Qi QW. Current situation and development of prenatal diagnosis in China[J]. Front Med China,2010,4:271-274.
[5]Kaur A,Singh JR. Chromosomal abnormalities:genetic disease burden in India[J]. Int J Hum Genet,2010,10:1-14.
[6]Verma IC. Burden of genetic disorders in India[J]. Indian J Pediatr,2000,67:893-898.
[7]Fan YS,Ouyang X,Peng J,et al. Frequent detection of parental consanguinity in children with developmental disorders by a combined CGH and SNP microarray[J]. Mol Cytogenet,2013,6:38
[8]Wiszniewska J,Bi W,Shaw C,et al. Combined array CGH plus SNP genome analysesin a single assay for optimized clinical testing[J]. Eur J Hum Genet,2014,22:79-87
[9]Howard HJ,Beaudet A,Gil-da-Silva Lopes V,et al. Diseasespecific databases:why we need them and some recommendations from the Human Variome Project Meeting,May 28,2011[J]. Am J Med Genet A,2012,158A:2763-2766.
[10] Estroff JA. Prenatal diagnosis and imaging of genetic syndromes[J].Semin Roentgenol,2004,39(2):323-335.
[11] Le Caignec C,Boceno M,Saugier-Veber P,et al. Detection of genomic imbalances by array based comparative genomic hybridization in fetuses with multiple malformations[J].J Med Genet,2005,42(2):121-128.
[12] Stewart T L. Screening for aneuploidy:the genetic sonogram[J].Obstetrics and Gynecology Clinics of North America,2004,31(1):21-33.
[13] Jansen F A,Blumenfeld Y J,Fisher A,et al. Array Comparative Genomic Hybridization and Fetal Congenital Heart Defects-A systematic review and meta-analysis[J].Ultrasound Obstet Gynecol,2014.
[14]李胜利,朱军.胎儿畸形产前超声诊断学[M].北京:人民军医出版社,2015.
[15] PalumboO,FischettoR,PalumboP,etal.Denovo microduplication of CHL1 in a patient with non-syndromic developmental phenotypes[J].Mol Cytogenet,2015,8:66. doi:10.1186/s13039-015-0170-3.
[16] Al Dhaibani MA,Allingham-Hawkins D,El-Hattab AW.De novo chromosome 7q36.1q36.2 triplication in a child with developmental delay,growth failure,distinctive facial features,and multiple congenital anomalies:a case report[J].BMC Med Genet,2017,18(1):118. doi:10.1186/s12881-017-0482-8.
[17] Courtens W,Wuyts W,Rooms L,et al.A subterminal deletion of the long arm of chromosome 10:a clinical report and review[J].Am J Med Genet A,2006,140(4):402-9.
[18] Onesimo R,Orteschi D,Scalzone M,et al.Chromosome 9p deletion syndrome and sex reversal:novel findings and redefinition of the critically deleted regions[J].Am J Med Genet A,2012,158A(9):2266-71.doi:10.1002/ajmg.a.35489.
[19] Nagamani SC,Erez A,Eng C,et al.Interstitial deletion of6q25.2-q25.3:a novel microdeletion syndrome associated with microcephaly,developmental delay,dysmorphic features and hearing loss[J].Eur J Hum Genet,2009,17(5):573-81. doi:10.1038/ejhg. 2008. 220.
[20] Ronzoni L,Tagliaferri F,Tucci A,et al. Interstitial 6q25microdeletion syndrome:ARID1B is the key gene[J].Am J Med Genet A.2016,170A(5):1257-61.doi:10.1002/ajmg.a.37553.
[2]Callaway JL,Shaffer LG,Chitty LS,et al. The clinical utility of microarray technologies applied to prenatal cytoge-netics in the presence of a normal conventional karyotype:a review of the literature[J]. Prenat Diagn,2013,33:1119e1123.
[3]Schwartz S. Clinical utility of single nucleotide polymorphism arrays[J]. Clin Lab Med,2011,31:581-594.
[4]Bian XM,Guo Q,Qi QW. Current situation and development of prenatal diagnosis in China[J]. Front Med China,2010,4:271-274.
[5]Kaur A,Singh JR. Chromosomal abnormalities:genetic disease burden in India[J]. Int J Hum Genet,2010,10:1-14.
[6]Verma IC. Burden of genetic disorders in India[J]. Indian J Pediatr,2000,67:893-898.
[7]Fan YS,Ouyang X,Peng J,et al. Frequent detection of parental consanguinity in children with developmental disorders by a combined CGH and SNP microarray[J]. Mol Cytogenet,2013,6:38
[8]Wiszniewska J,Bi W,Shaw C,et al. Combined array CGH plus SNP genome analysesin a single assay for optimized clinical testing[J]. Eur J Hum Genet,2014,22:79-87
[9]Howard HJ,Beaudet A,Gil-da-Silva Lopes V,et al. Diseasespecific databases:why we need them and some recommendations from the Human Variome Project Meeting,May 28,2011[J]. Am J Med Genet A,2012,158A:2763-2766.
[10] Estroff JA. Prenatal diagnosis and imaging of genetic syndromes[J].Semin Roentgenol,2004,39(2):323-335.
[11] Le Caignec C,Boceno M,Saugier-Veber P,et al. Detection of genomic imbalances by array based comparative genomic hybridization in fetuses with multiple malformations[J].J Med Genet,2005,42(2):121-128.
[12] Stewart T L. Screening for aneuploidy:the genetic sonogram[J].Obstetrics and Gynecology Clinics of North America,2004,31(1):21-33.
[13] Jansen F A,Blumenfeld Y J,Fisher A,et al. Array Comparative Genomic Hybridization and Fetal Congenital Heart Defects-A systematic review and meta-analysis[J].Ultrasound Obstet Gynecol,2014.
[14]李胜利,朱军.胎儿畸形产前超声诊断学[M].北京:人民军医出版社,2015.
[15] PalumboO,FischettoR,PalumboP,etal.Denovo microduplication of CHL1 in a patient with non-syndromic developmental phenotypes[J].Mol Cytogenet,2015,8:66. doi:10.1186/s13039-015-0170-3.
[16] Al Dhaibani MA,Allingham-Hawkins D,El-Hattab AW.De novo chromosome 7q36.1q36.2 triplication in a child with developmental delay,growth failure,distinctive facial features,and multiple congenital anomalies:a case report[J].BMC Med Genet,2017,18(1):118. doi:10.1186/s12881-017-0482-8.
[17] Courtens W,Wuyts W,Rooms L,et al.A subterminal deletion of the long arm of chromosome 10:a clinical report and review[J].Am J Med Genet A,2006,140(4):402-9.
[18] Onesimo R,Orteschi D,Scalzone M,et al.Chromosome 9p deletion syndrome and sex reversal:novel findings and redefinition of the critically deleted regions[J].Am J Med Genet A,2012,158A(9):2266-71.doi:10.1002/ajmg.a.35489.
[19] Nagamani SC,Erez A,Eng C,et al.Interstitial deletion of6q25.2-q25.3:a novel microdeletion syndrome associated with microcephaly,developmental delay,dysmorphic features and hearing loss[J].Eur J Hum Genet,2009,17(5):573-81. doi:10.1038/ejhg. 2008. 220.
[20] Ronzoni L,Tagliaferri F,Tucci A,et al. Interstitial 6q25microdeletion syndrome:ARID1B is the key gene[J].Am J Med Genet A.2016,170A(5):1257-61.doi:10.1002/ajmg.a.37553.