The Application of SNP Microarray Technique in Fetal Central Nervous System Abnormality

Author(s): Conghong Xu, Yuanzhen Zhu, Jingyi Liu, Changhong Yu, Huafeng Li

Objective: To explore the application significance of SNP microarray technique in fetal central nervous system deformity and the relationship between chromosome abnormality and fetal nervous system abnormality. Methods: Collection of 40 abnormal amniotic fluid and abortion casese of fetal nervous system abnormalities sereened by Ultrasonic testing and Nuclear magnetic resonance (NMR) were tested by SNP microarray technology, of the 40 samples, 32 samples of amniotic fluid were additionally analyzed with traditional karyotype. Results: The success rate of fetal nervous system anomaly detection was 100%. At the same time, in 32 cases of amniotic fluid analysis, 31 cases were successfully cultured, and the success rate was 96.9%. There were 7 cases of chromosome abnormality (17.5%), 2 cases with abnormal number(5%), 5 cases of structural abnormalities（12.5%）.32 samples of amniotic fluid were tested both by traditional karyotype analysis and SNP microarray technique, the traditional karyotype analysis only found 2 cases of numerical chromosomal abnormalities. SNP chromosome microarray technology also found 2 cases structura1 chromosomal abnormalities in the sample of lateral ventricle and hydrocephalus. Additonally detected out 3 cases of structura1 chromosomal abnormalities among 8 cases of abortion samples with fetal nervous system abnormality. Conclusion: SNP microarray can not only detect the numerical abnormalities of chromosome and large fragments of structural abnormalities, but also detect the microdeletion and microduplation of chromosomes, so as to help fully understanding the status of the chromosomal abnormalities of fetal nervous system abnormality, Particularly, gene copy number variation (CNV) is closely related to fetal central nervous system abnormality.

Fetal Central Nervous Malformation, SNP Microarray, Chromosome Number/Structure Abnormality, Gene Copy Number Variation

1. PetracchiF,CrespoL,MichiaC,etal．Holoprosencephaiy at prental diagnosis：analysis of 28 cases regarding etiopathogenic diagnoses [J].prenatai diagn,2011,31（9）887-891.
2. JHuang, I. Y. M. Wah, R. K. Pooh,ealt. Molecular genetics in fetal neurology[J]. Seminars in Fetal and Neonatal Medicine, 2012,17(6):341–346.
3. F. Petracchi, L. Crespo, C.Michia, ealt. GadowHoloprosencephaly at prenatal diagnosis: analysis of 28 cases regarding etiopathogenic diagnoses,” [J]. PrenatalDiagnosis,2011,31(9): 887–89.
4. Yunan Wang, Jian Lu, An wei.,etal. Analysis of chromosome microarray of abnormal fetus in nervous system [J]. China prenatal diagnostic journal (electronic edition),2016,8(4):35-42.
5. Lathi RB, Loring M, Massie JAM, et al. Informatics Enhanced SNP Microarray Analysis of 30 Miscarriage Samples Compared to Routine Cytogenetics[J]. PLoS ONE, 2012, 7(3): e31282.
6. Hai ming Yuan, Meng fan Chen, Xiaoyan Deng, etal. Application of chromosome microarray technique in the diagnosis of spontaneous abortion [J]. Chinese journal of genetics,2016,33 (4) : 442-445.
7. Spitsyn MA , Shershov VE, Kuznetsova VE. Infrared fluorescent markers for microarray DNA analysis on biological microchip[J]. Mol Biol（Mosk）,2015,49（5）：760 -769.
8. D. Onkar, P. Onkar, and K. Mitra, Evaluation of fetal centralnervous system anomalies by ultrasound and its anatomical corelation [J]. Journal of Clinical and Diagnostic Research, 2014. ,8(6):5-7.
9. FranekKJ,ButlerJ,JohnsonJ.Deletion of the immunoglobulin domain of IL1RAPL1 results in nonsyndromic X-linked intellectual disability associated with behavioral problems and mild dysmorphism[J]. Am. J. Med. Genet. 2011,155A（5）: 1109-1114
10. Melissa T Carter, Stephanie A St. Pierre, Elaine H Zackai, etal. Phenotypic Delineation of Emanuel Syndrome (Supernumerary Derivative 22 syndrome): Clinical features of 63 individuals[J]. Am J Med Genet A.,2009, 149A(8): 1712–1721.
11. Halil Aslan, Nilay Karaca, Seher Basaran,Prenatal diagnosis of Wolf-Hirschhorn syndrome (4p-) in association with congenital hypospadias and foot deform[J]. BMC Pregnancy and Childbirth, 2003 1（24）:1471-2391.
12. Feng Y, Walsh CA. Mitotic spindle regulation by Nde1 controls cerebral cortical size[J]. Neuron,2004,44(2):279–93.
13. Alkuraya FS, Cai X, Emery C, Mochida GH, Al-Dosari MS, Felie JM, etal. Human mutations in NDE1 cause extreme microcephaly with lissencephaly [corrected] [J]. Am J Hum Genet. 2011;88(5):536–47.