The use of chromosomal microarray analysis for diagnostics of chromosomal pathology in fetal central nervous system malformations
Abstract
Introduction. The prevalence of congenital malformations (CMFs) in fetal central nervous system (CNS) ranges from 1.5 to 3 % and covers around 29 % among all malformations, whereas percentage in the structure of perinatal and infant mortality reaches 25–26 %.
Aim: to estimate frequency of pathogenic copy number variations (CNVs) in fetuses with congenital malformations of CNS and normal karyotyping cytogenetic analysis.
Materials and Methods. There were enrolled 42 pregnant women underwent invasive prenatal diagnostics in 2013–2019 due to ultrasound detection of congenital CNS defect in fetus. Fetal samples were studied by using chromosome microarray analysis (CMA).
Results. Various pathogenic CNVs were detected in 7 (16.6 %) fetuses with prenatally diagnosed congenital CNS malformations. Non-syndrome pathogenic CNVs were detected in 85.7 %.
Conclusion. Thus, performing chromosome microarray analysis as the first-line assay allows to diagnose not only aneuploidy, but also microdeletion/microduplication, the size of which below resolution threshold for standard cytogenetic karyotyping
About the Authors
J. K. Kievskaya
Genomed LTD
Russian Federation
Russian Federation
Julia K. Kievskaya – MD, Geneticist
bild. 5, Podolskoe Highway, Moscow, 115093, Russia
I. V. Kanivets
Genomed LTD; Russian Medical Academy of Continuous Professional Education, Health Ministry of Russian Federation
Russian Federation
Russian Federation
Ilya V. Kanivets – MD, PhD, Geneticist,
bild. 5, Podolskoe Highway, Moscow, 115093, Russia
2/1 buil. 1, Barrikadnaya Str., Moscow 123995, Russia
E. V. Kudryavtseva
Ural State Medical University, Health Ministry of Russian Federation
Russian Federation
Russian Federation
Elena V. Kudryavtseva – MD, PhD, Obstetrician-Gynecologist, Associate Professor, Department of Obstetrics and Gynecology
3 Repin Str., Еkaterinburg 620219, Russia
D. V. Pyankov
Genomed LTD
Russian Federation
Russian Federation
Denis V. Pyankov – MD, Laboratory Geneticist, Head of Laboratory of Molecular Pathology
bild. 5, Podolskoe Highway, Moscow, 115093, Russia
S. A. Korostelev
Genomed LTD
Russian Federation
Russian Federation
Sergey A. Korostelev – MD, Dr Sci Med, Professor, Director General
bild. 5, Podolskoe Highway, Moscow, 115093, Russia
References
1. ISUOG Guidelines. Sonographic examination of the fetal central nervous system: guidelines for performing the 'basic examination' and the 'fetal neurosonogram'. Ultrasound Obstet Gynecol. 2007;29:109–16. https://doi.org/10.1002/uog.3909.
2. Demikova N.S., Podolskaya M.A., Lapina A.S., Asanov A.Yu. Impact of prenatal diagnosis and selective abortion on the frequency of congenital malformations. [Vliyanie prenatal'noj diagnostiki i selektivnyh preryvanij beremennosti na chastotu vrozhdennyh porokov razvitiya]. Akusherstvo i ginekologiya. 2017;(7):130–5. (In Russ.). https://doi.org/10.18565/aig.2017.7.130-5.
3. Simakhodskiy A.S., Romanenko O.P. The effticiency of diagnosis and treatment of congenital malformations in St. Petersburg over 2006- 2015. [Effektivnost' diagnostiki i lecheniya vrozhdennyh porokov razvitiya v Sankt-Peterburge za 2006-2015 gg]. Rossijskij pediatricheskij zhurnal. 2017;20(4):214–7. (In Russ.). https://doi.org/10.18821/1560-9561-2017-20-4-214-217.
4. Morozova E.A., Sergeeva R.R., Morozov D.V. Practical aspects of diagnosis and treatment of neonatal seizures. [Sovremennye problemy diagnostiki i lecheniya neonatal'nyh sudorog]. Epilepsiya i paroksizmal'nye sostoyaniya. 2018;10(4):17–25. (In Russ.). https://doi.org/10.17749/2077-8333.2018.10.4.017-025.
5. Zavadenko A.N., Medvedev M.I., Degtyareva M.G. et al. Etiologies of neonatal seizures in infants of different gestational age. [Prichiny neonatal'nyh sudorog u detej razlichnogo gestacionnogo vozrasta]. Epilepsiya i paroksizmal'nye sostoyaniya. 2018;10(3):19–30. (In Russ.). https://doi.org/10.17749/2077-8333.2018.10.3.019-030
6. Kozhanova T.V., Zhilina S.S., Meshcheryakova T.I. et al. Mutation in the ALD H7A1 gene in a patient with pyridoxal phosphate-dependent neonatal epileptic encephalopathy: a clinical case. [Mutaciya v gene ALD H7A1 u pacienta s piridoksin-zavisimoj neonatal'noj epilepticheskoj encefalopatiej: klinicheskij sluchaj]. Epilepsiya i paroksizmal'nye sostoyaniya. 2019;11(1):70–8. (In Russ.). https://doi.org/10.17749/2077-8333.2019.11.1.70-78.
7. Huang J., Wah I.Y.M., Pooh R.K., Choy K.W. Molecular genetics in fetal neurology. Semin Fetal Neonatal Med. 2012;17(6):341–6. https://doi.org/10.1016/j.siny.2012.07.007.
8. Petracchi F., Crespo L., Michia C. et al. Holoprosencephaly at prenatal diagnosis: analysis of 28 cases regarding etiopathogenic diagnoses. Prenat Diagn. 2011;31(9):887–91. https://doi.org/10.1002/pd.2796.
9. Goetzinger K.R., Stamilio D.M., Dicke J.M., Macones G.A. Evaluating the incidence and likelihood ratios for chromosomal abnormalities in fetuses with common central nervous system malformations. Am J Obstet Gynecol. 2008;199(3):285.e1–6. https://doi.org/10.1016/j.ajog.2008.06.100.
10. Evangelidou P., Sismani C., Ioannides M. et al. Clinical application of whole-genome array CGH during prenatal diagnosis: study of 25 selected pregnancies with abnormal ultrasound findings or apparently balanced structural aberrations. Mol Cytogenet. 2010;3:24. https://doi.org/10.1186/1755-8166-3-24.
11. Ginter E.K., Zolotukhina T.V., Antonenko V.G. et al. Cytogenetic methods for the diagnosis of chromosomal diseases: methodological guide for doctors. [Citogeneticheskie metody diagnostiki hromosomnyh boleznej: Metodicheskoe posobie dlya vrachej]. Moskva: RMAPOMGNC, 2009. 82 s. (In Russ.).
12. Wapner R.J., Martin C.L., Levy B. et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med. 2012;367(23):2175–84. https://doi.org/10.1056/NEJMoa1203382.
13. Bui T-H., Vetro A., Zuffardi O., Shaffer L.G. Current controversies in prenatal diagnosis 3: is conventional chromosome analysis necessary in the post-array CGH era? Prenat Diagn. 2011;31(3):235–43. https://doi.org/10.1002/pd.2722.
14. Friedman J.M. High-resolution array genomic hybridization in prenatal diagnosis. Prenat Diagn. 2009;29(1):20–8. https://doi.org/10.1002/pd.2129.
15. Vestergaard E.M., Christensen R., Petersen O.B., Vogel I. Prenatal diagnosis: array comparative genomic hybridization in fetuses with abnormal sonographic findings. Acta Obstet Gynecol Scand. 2013;92(7):762–8. https://doi.org/10.1111/aogs.12146.
16. Kievskaya J.K., Shilova N.V., Kanivets I.V. et al. The use of chromosomal microarray analysis for the diagnosis of chromosomal pathology in fetuses with congenital malformations of heart. [Primenenie hromosomnogo mikromatrichnogo analiza dlya diagnostiki hromosomnoj patologii u plodov s vrozhdennymi porokami serdca]. Ural'skij medicinskij zhurnal. 2019;(15):18–22. (In Russ.). https://doi.org/10.25694/URMJ.2019.15.06.
17. D'Amours G., Kibar Z., Mathonnet G. et al. Whole-genome array CGH identifies pathogenic copy number variations in fetuses with major malformations and a normal karyotype. Clin Genet. 2012;81(2):128–41. https://doi.org/10.1111/j.1399-0004.2011.01687.
18. Kearney H.M., Thorland E.C., Brown K.K. et al.; Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med. 2011;13(7):680–5. https://doi.org/10.1097/GIM.0b013e3182217a3a.
19. Sun L., Wu Q., Jiang S-W. et al. Prenatal diagnosis of central nervous system anomalies by high-resolution chromosomal microarray analysis. Biomed Res Int. 2015;2015:426379. https://doi.org/10.1155/2015/426379.
20. Wapner R.J., Martin C.L., Levy B. et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. New Engl J Med. 2012;367(23): 2175–84. https://doi.org/10.1056/NEJMoa1203382.
Review
For citations:
Kievskaya J.K., Kanivets I.V., Kudryavtseva E.V., Pyankov D.V., Korostelev S.A. The use of chromosomal microarray analysis for diagnostics of chromosomal pathology in fetal central nervous system malformations. Obstetrics, Gynecology and Reproduction. 2020;14(4):449-456. (In Russ.) https://doi.org/10.17749/2313-7347/ob.gyn.rep.2020.160
Views: 475
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Email this article 
