Cytogenetic Investigation in Prenatal Specimecimens for Effective Prognosis of Pregnancy Related Complications
American Journal of Biomedical and Life Sciences
Volume 2, Issue 2, April 2014, Pages: 46-54
Received: Apr. 22, 2014; Accepted: May 14, 2014; Published: May 30, 2014
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Binay Kumar Raut, Department of Biochemistry, Kathmandu University School of Medical Sciences, Dhulikhel, Kavre, Nepal
Lakshman Kumar Balasubramanian, Department of Biotechnology, Kongunadu Arts and Science College, Coimbatore, Tamilnadu, India
Mukesh Kumar Jha, Department of Physiology, Kathmandu University School of Medical Sciences, Dhulikhel, Kavre, Nepal
Shyam Sundar Malla, Department of Biochemistry, Kathmandu University School of Medical Sciences, Dhulikhel, Kavre, Nepal
Moka Rajasekhar, Department of Biotechnology, School of Life Sciences, Manipal University, Manipal, Karnataka, India
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Background: Alterations in chromosomal content of mother and infant are central characteristics of various complications related to pregnancy and early childhood. About 60% of the pregnancy losses, 2-3% of all the neonates and 50% of childhood deafness, blindness, mental retardation and 1 to 10 % of all the malignancies are directly due to genetic factors. Hence cytogenetic testing of pre and post natal samples can prove to be useful for discovery of non-invasive markers for prevention of such conditions beforehand. Aim of the study: The present study was carried out to detect numerical and structural abnormalities in 56 subjects with repeated miscarriages, bad obstetric history and sub fertility by analysing peripheral blood, products of conception (POC) material, and recovered cell lines from prenatal samples. Methods: Conventional cytogenetics: Peripheral blood culture (PBC) supplemented with mitogen Phytohemagglutinin (PHA), metaphase chromosomes was harvested after 72 hours for chromosome analysis. Tissue cytogenetics: Culture of solid tissue was used as a source for mitotic cells from products of conception (POC) from first trimester spontaneous abortions for aneuploidy detection; and Prenatal chromosome analysis was performed by either chorionic villus sampling (CVS), amniotic fluid and cord blood after culture. Image acquisition and analysis was performed by using automated karyotyping (IKAROS) software based on G, C and R banding. Results: Chromosomal abnormalities were located in all types of specimens but were predominantly observed in recurrent pregnancy loss (RPL) and product of conception (POC) samples. Aberrations observed were mainly translocations, satellites, additions in RPL cases like 46,XX with instances of (D/D,D/G,G/Gassociations);45,XX,rob(13;14);46,XXt(4;21);46,XX,(9qh+);46,XX,(14ps+);46,XX, t(5;6) and ploidy involving 67,XX+;64,XXX+;69,XXX;63,XXX;58,XX+ in the POC cases. Conclusion: Cytogenetic screening could provide to be a useful method for monitoring patients with abnormal pregnancies. The cytogenetic result is an independent prognostic indicator, with certain karyotypes associated with a good prognosis for the better treatment.
Products of Conception (POC), Peripheral Blood Culture (PBC), Karyotyping (G, C and R Banding)
To cite this article
Binay Kumar Raut, Lakshman Kumar Balasubramanian, Mukesh Kumar Jha, Shyam Sundar Malla, Moka Rajasekhar, Cytogenetic Investigation in Prenatal Specimecimens for Effective Prognosis of Pregnancy Related Complications, American Journal of Biomedical and Life Sciences. Vol. 2, No. 2, 2014, pp. 46-54. doi: 10.11648/j.ajbls.20140202.13
Alter BP. Clinical features of Fanconi’s anaemia. In: Young NS, Alter BP, eds. Aplastic anemia: acquired and inherited. Philadelphia: Saunders, 1994:275-308.
Amor-Gueret M. Bloom’s syndrome. Orphanet encyclopedia. [cited on 2004. Available from: ttp//
Andaloussi El and Bilhou-Nabera C (2007) Case Report New Complex Chromosomal Translocation in Chronic Myeloid Leukaemia: t(9;18;22)(q34;p11;q11) J. Biomedicine and Biotechnology Vol 2007, Article ID 92385, 3 pages.
Arrighi FE and Hsu TE (1971) Localization of heterochromatic regions of human chromosomes. Cytogenetics 10; 81-86.
Auerbach, A D., Adler, B., and Chaganti, R. S. K. (1981). Prenatal and postnatal diagnosis and carrier detection of Fanconi anemia by the cytogenetic method. Pediatrics, 67, 128-35.
Auerbach, A. D., Buchwald, M., and Joenje, H. (2001). Fanconi anemia. In: The Metabolic and Molecular Bases of Inherited Disease,(Eds. CR Scriver, WS Sly, B Childs, et al.), 1, 753-68 McGraw-Hill, New York.
Bagby, G. C., Lipton, J. M., Sloand, E. M., and Schiffer, C. A. (2003).Marrow failure. J. Med. Genet., 40, 1-10.
Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Sultan C. (1952) Proposals for the classification of the myeloidysplastic syndrome. Br J Hematol 1952; 51: 189-199
Bloom D (1954) Congenital telangeetatic erythema resembling lupus erythematosus in dwarfs. Am J. Dis child 88; 754-758.
Brady K, Duff P, Harlass FE, Reid S (1991). Role of amniotic fluid cytogenetic analysis in the evaluation of recent fetal death Am J Perinatol;8(1):68-70.
Carp H, Feldman B, Oelsner G, Schiff E. (2004) Parental karyotype and subsequent live births in recurrent miscarriage. Fertil Steril 81; 1296-1301.
Carp H, Toder V, Aviram A, Daniely M, Mashiach S and Barkai G (2001) Karyotype of the abortus in recurrent miscarriage. Fertil Steril 75,678–682.
Carrera M (2001) Screening prenatal de aneuploidı´as: QF-PCR y FISH. Prog Diag Prenat 13,262–266.
Caspersson T, Zech L, Johansson C: Dif-ferential binding of alkylating fluorochromes in human chromosomes. Exp Cell Res 1970, 60:315-319.
Chandley AC (1983). Infertility and recurrent abortion In. Emery AEH, Rimoin (Eds). Principles and practice of Medical genetics, Churchill Livingston, New York.
de Braekeleer M (1987) “Variant Philadelphia translocations in chronic myeloid leukemia,” Cytogenetics and Cell Genetics, vol. 44, no. 4, pp. 215–222, 1987.
Dicken CH, Dewald G, and Gordon H (1978) Sister chromatid exchanges in Bloom syndrome. Arch Dermatol 114(5); 755-760.
Dutrillaux B (1973) Nouveau systeme de marquage Chromosomeiqe les bandes T. Chromosoma 41; 395;402.
Eisenberg B, Wapner RJ (2002) Clinical procedures in prenatal diagnosis. Best Pract Res Clin Obstet Gynaecol 16:611–627.
Ellis NA, German J. Molecular genetics of Bloom’s syndrome. Hum Mol Genet 1996;5:1457-63.
Fred Kavalier (2005) Investigation of recurrent miscarriages BMJ. 2005 July 16; 331(7509): 121–122.
Fryns JP, Kleczkowska A, Kubien E, Petit P, Vanberghe H (1984) Cytogenetic survey in couples with recurrent fatal wastage. Hum Genet 65;336-354.
German J and Crippa LP (1966) chromosomal breakage in diploid cell lines from Bloom’s syndrome and Fanconi’s anemia. Ann Genet 9: 143-154.
Goodpasture C Bloom SE, Hsu TC and Arrighi FE (1975) Human nucleolus organizers: the satellites or the stalks? Am J Hum Genet 28;;559-566.
Hassold, T. and Chiu, D. (1985) Maternal age specific rates of numerical chromosome abnormalities with special reference to trisomy. Hum. Genet., 70, 11–17.
Hatice Ilgin, Ayse Nurten Akarsu, Fatma Isik Bökesoy (1999) Cytogenetic and Phenotypic Findings in Turkish Patients With Fanconi’s Anemia Tr. J. of Medical Sciences 29; 151-154
Horrike S, Taniwaki M, Misawa S, Abe T (1988) Chromosome abnormalities and karyotypic evolution 83 patients with myelodysplastic syndrome and predictive value for prognosis. Cancer 62: 1129-38.
Hossein Mozdarani, Anahita Mohseni Meybodi, Shabnam Zari-Moradi (2008) A cytogenetic study of couples with recurrent spontaneous abortions and infertile patients with recurrent IVF/ICSI failure. Indian J of Hum Genet 14(1) 1-6.
Hsu, T. C. Mammalian chromosomes in vitro, I. Karyotype of man. Journal of Heredity 43, 167–172 (1952).
Jacobs P.A. and Hassold T.J. (1987) Chromosome abnormalities: origin and etiology in abortions and live births. In Vogal, F. and Sperling, K. (eds), Human Genetics. Springer-Verlag, Berlin, pp. 233–244.
Jacobs RH, Cornbleet MA, Vardiman JW, Larson RA, Le Beau MM, Rowley JD(1986) Prognostic implications of morphology and karyotype in primary myelodysplastic syndromes. Blood 67:1765-72.
Jemal A, Thomas A, Murray T, Thun M (2002). "Cancer statistics, 2002". CA Cancer J Clin 52 (1): 23–47.
Jim Martin Southern Ontario Fertility Technologies (S.O.F.T.) 555 Southdale Rd., E., Suite 107, London, Ontario, N6E 1A2.
Joenje H, Oostra AB, Wijker M, Di SFM, Van BCG, Rooimans MA, Ebell W, Van WM, Pronk JC, Buchwald M, Arwert F (1997). Evidence for at least eight Fanconi anemia genes. Am J Hum Genet;61:940-944.
Kadam PR, Nangangund GJ, Advani SH (1990), The occurrence of variant Ph translocation in chronic myeloid leukemia (CML); a report of 6 cases. Hematol Oncol 8; 303-312.
Kalousek, D.K., Pantzar, T., Tsai, M. et al. (1993) Early spontaneous abortion: morphologic and karyotypic findings in 3,912 cases. Birth Defects, 29, 53–61.
Kim JM, Sim AS, Lee EH (2006) Amniotic chromosome analysis in pregnant women identified by triple marker testing as screens positive. Korean J Lab Med 26(2); 123-30.
Lerardi-Curto L (2009) Chromosomal breakage syndromes. eMedicine Pediatrics, Webmed.
Marquard K, Westphal LM, Milki AA and Lathi RB (2009) Etiology of recurrent pregnancy loss in women over the age of 35 years. Fertil Steril 30th July 2009.
Mitelman F (1993), “The cytogenetic scenario of chronic myeloid leukemia,” Leukemia and Lymphoma, vol. 11, pp. 11–15, 1993.
Mitelman F, Johansson B, and Mertens F (2006). Eds, “Mitelman Database of Chromosome Aberrations in Cancer,” http://cgap, August 2006.
Moorhead, P.S., Nowell, P.C., Mellman, W.J., Battips, D.M. and Hungereford, D.A. (1960). Chromosome preparations of leukocytes cultured from human peripheral blood. Exp. Cell Res. 20: 613-616.
Naeimeh Tayebi, Hossain Khodaei (2008) Bloom’s syndrome in a 12-year-old Iranian girl Ind J. Hum Genet 14(3); 103-105.
Nowell, P., & Hungerford, D. A minute chromosome in human chronic granulocytic leukemia. Science 132, 1497 (1960).
Ogasawara M, Ozaki Y, Sato T, Suzumori N, Suzumori K (2004) Poor prognosis of recurrent aborters with either maternal or paternal reciprocal translocations. Fertil Steril 81;367-373.
Reid DE, Ryan KJ, Benirsche K. (1972) Principles and management of human reproduction, Saunders, Philadelphia, London, Toronto.
Rowley JD (1973) “A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining,” Nature, vol. 243, no. 5405, pp.290–293, 1973.
Sandberg A. A (1980) The Chromosomes in Human Cancer and Leukemia, Elsevier North Holland, New York, NY, USA, 1980.
Sanja cirkovic, Marija Guc-Scekic, Dragana Vujic and D micic (2006) Cytogenetic diepoxybutane sensitivity in Serbian children with Fanconi anemia. Arch Biol Sci Belgrade. 58 (4); 215-219.
Santalo J, Catala V and Badenas J (1987) Chromosomal abnormalities and IVF. In Egozcue J (ed.) Cellular Aspects of In Vitro Fertilization. Cell Biology Reviews. Leiola, pp. 63–72.
Schoch C and Haferlach T (2007) Cytogenetics in acute myeloid leukemia. Current Oncology Report vol. 4(5) 390-391.
Schroeder TM, Tilgen D, Kruger J, Vogel F. Formal genetics of Fanconi’s anemia. Hum Genet 1976;32:257-88.
Seabright M (1971) A rapid banding technique for human chromosomes. Lancet, 7731:971-972.
Shaffer LG, Tommerup N, ISCN 2005: An international system for cytogenetic nomenclature. S. Karger, Basel, Switzerland 2005.
Shahrabani-Gargir L, Shomrat R, Yaron Y, Orr-Urtreger A, Groden J, Legum C. High frequency of a common bloom syndrome Ashkenazi mutation among Jews of polish origin Genet Test 1998;2:293-6.
Shalev E, Zalel Y, Weiner E, Cohen H, Shneur Y (1994) The role of cordocentesis in assessment of mosaicism found in amniotic fluid cell culture. Acta Obstet Gynecol Scand; 73(2):119-22.
Tjio, J. H., & Levan, A. The chromosome number of man, Hereditas 42, 1–6 (1956)
Toogeh Gl, Najafi AH, and Keyhani M (2003) Cytogenetic findings in acute myeloid leukemia. Acta Medica Iranica 41 (4) 227-232.
Verma RS, Babu A (1994) Human chromosomes: principles and techniques, 2nd edn McGraw-Hill, New York.
Vundinti BR, Kerketta L, Jijina F and Ghosh K (2009) Cytogenetic study of myelodysplastic syndrome from India. Indian J Med Res 130: 155-159.
Warburton D, Stein Z, Kline J, and Susser M, et al. (1980) Chromosome abnormalities in spontaneous abortion: data from the New York City study. In Porter IH and Hook EB (eds) Human Embryonic and Fetal Death. Academic Press, New York, pp. 261–287.
Wegner RD (1999) Diagnostic cytogenetics. Springer, Berlin.
Yunis JJ: High resolution of human chromosomes. Science 1976, 191:1268-1270.
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