OJPed  Vol.1 No.4 , December 2011
Mechanism of origin in two cases of chimerism
ABSTRACT
Chimerism is defined as the presence in a subject of more than one stable and genetically distinct cell line; cases reported so far include both patients with ambiguous genitalia and healthy subjects. The biological mechanisms, which may give origin to chimeras, are complex, and can be understood by analyzing DNA samples of the patients and their parents using molecular techniques. The objective of this study is to identify the mechanism of origin for the 2 cases we report. The first patient is a phenotipically normal girl with normal (external and internal) genitalia; the second patient had ambiguous genitalia and underwent surgery. DNA was purified from blood samples and, limited to Patient 1, from a sample of biliary cyst. Short tandem repeat polymorphisms were analyzed in order to identify the relative parental contribution to the patients. Molecular analyses carried out on the first patient are not fully informative because of two possible explanations (i.e. parthenogenetic and andrognetic chimera), while in the second case the presence of four alleles at some markers allowed us to identify a tetragametic chimera originnated from the fusion of two distinct embryos. Studies carried on one single tissue may not always be conclusive as they do not allow the precise identification of the mechanism of origin. In these cases, studies on more tissues are strongly suggested.

Cite this paper
nullMinelli, A. , Guala, A. , Groppo, A. , Restagno, G. , Lala, R. , Einaudi, S. , Repici, M. , Merlini, E. , Sbaiz, L. , Asnaghi, V. , Lopez, A. , Angellotti, P. , Cristina, S. and Danesino, C. (2011) Mechanism of origin in two cases of chimerism. Open Journal of Pediatrics, 1, 79-86. doi: 10.4236/ojped.2011.14019.
References
[1]   Koenigsberg, R. (Ed.) (1994) Churchill’s Medical Dictionary. Centro Scientifico Editore, 355.

[2]   Ramsay, M., Pfaffenzeller, W., Kotze, E., Bhengu, L. and Essop, F. (2009) Chimerism in black southern african patients with true hermaphroditism 46,XX/47XY,+21 and 46,XX/46,XY. Annals of the New York Academy of Sciences, 1151, 68-76. doi:10.1111/j.1749-6632.2008.03570.x

[3]   Malan, V., Vekemans, M. and Turleau, C. (2006) Chimera and other fertilization errors. Clinical Genetics, 70, 363-373. doi:10.1111/j.1399-0004.2006.00689.x

[4]   Makrydimas, G., Sebire, N., Thornton, S., Zagorianakou, N. and Lolis, D. (2002) Complete hydatidiform mole and normal live birth: A novel case of confined placental mosaicism: Case report. Human Reproduction, 17, 2459- 2463. doi:10.1093/humrep/17.9.2459

[5]   Golubovsky, M.D. (2003) Postzygotic diploidization of triploids as a source of un usual cases of mosaicism, chimerism and twinning. Human Reproduction, 18, 236- 242. doi:10.1093/humrep/deg060

[6]   Green, A., Barton, D., Jenks, P., Pearson, J. and Yates, J. (1994) Chimaerism shown by cytogenetics and DNA polymorphism analysis. Journal of Medical Genetics, 31, 816-817. doi:10.1136/jmg.31.10.816

[7]   Uehara S., Nata M., Nagae M., Sagisaka K. and Okamura K., (1995) Molecular biologic analyses of tetragametic chimerism in a true hermaphrodite with 46,XX/46,XY. Fertility and Sterilility, 63, 189-192.

[8]   Bonthron D.T., Strain L. and Dean J.C.S. (1997) Amalgamation of in vitro fertilized embryos, resulting in birth of a true hermaphrodite chimera. American Journal of Human Genetics, Supplement to Volume 61, A147.

[9]   Strain, L., Dean, J.C.S., Hamilton, M.P.R. and Bonthron, D. T. (1998) A true hermaphrodite chimera resulting from embryo amalgamation after in vitro fertilization. New England Journal of Medicine, 338, 166-169. doi:10.1056/NEJM199801153380305

[10]   Yu, N., Kruskall, M.S., Yunis, J.J., Knoll, J.H.M. and Uhl, L. (2002) Disputed maternity leading to identification of tetragametic chimerism. New England Journal of Medicine, 346, 1545-1552. doi:10.1056/NEJMoa013452

[11]   Drexler, C., Glock, B., Vadon, M., Staudacher, E. and Dauber, E.M. (2005) Tetragametic chimerism detected in a healthy woman with mixed field agglutination reactions in ABO blood grouping. Transfusion, 45, 698-703. doi:10.1111/j.1537-2995.2005.04304.x

[12]   Malan, V., Gesny, R., Morichon-Delvallez, N., Aubry, M. and Benachi, A. (2007) Prenatal diagnosis and normal outcome of a 46,XX/46,XY chimera: A case report. Human Reproduction, 22, 1037-1041. doi:10.1093/humrep/del480

[13]   Verdiani, S., Bonsignore, A., Casarino, L., Ferrari, G. and Zia, S. (2009) An unusual observation of tetragametic chimerism: Forensic aspects. International journal of legal medicine, 123, 431-435. doi:10.1007/s00414-009-0332-0

[14]   Giltay, J.C., Brunt, T., Beemer, F.A., Wit, J.M. and Ploos Van Amstel, H.K. (1998) Polymorphic detection of a parthenogenetic maternal and double paternal contribution to a 46,XX/46,XY hermaphrodite. The American Journal of Human Genetics, 62, 937-940. doi:10.1086/301796

[15]   Strain, L., Warner, J.P., Johnston, T. and Bonthron, D.T. (1995) A human parthenogenetic chimaera. Nature Genetics, 11, 164-169. doi:10.1038/ng1095-164

[16]   Chen, C.P., Chern, S.R., Sheu, J.C., Lin, S.P. and Hsu, C.Y. (2005) Prenatal diagnosis, sonographic findings and molecular genetic analysis of a 46,XX/46,XY true hermaphrodite chimera. Prenatal diagnosis, 25, 502-506. doi:10.1002/pd.1181

[17]   Draper, N.L., Conley, C., Smith, C. and Benson, K. (2008) Dispermic chimerism identified during HLA typing for stem cell transplantation. Transfusion, 48, 1398- 1402. doi:10.1111/j.1537-2995.2008.01711.x

[18]   Mosebach, M., Parkner, A., Jakubiczka, S., Wieacker, P. and Heim, M.U. (2006) Dispermic chimerism identified during blood group determination and HLA typing. Transfusion, 46, 1978-1981. doi:10.1111/j.1537-2995.2006.01005.x

[19]   Kaiser-Rogers, K.A., Mcfadden, D.E., Livasy, C.A., Dansereau, J. and Jiang, R. (2006) Androgenetic/biparental mosaicism causes placental mesenchymal dysplasia. Journal of Medical Genetics, 43, 187-192. doi:10.1136/jmg.2005.033571

[20]   Giurgea, I., Sanlaville, D., Fournet, J. C., Sempoux, C. and Bellanne-Chantelot, C. (2006) Congenital hyperinsulinism and mosaic abnormalities of the ploidy. Journal of Medical Genetics, 43, 248-254. doi:10.1136/jmg.2005.034116

[21]   Surti, U., Hill, L. M., Dunn, J., Prosen, T. and Hoffner, L. (2005) Twin pregnancy with a chimeric androgenetic and biparental placenta in one twin displaying placental mesenchymal dysplasia phenotype. Prenatal diagnosis, 25, 1048-1056. doi:10.1002/pd.1255

[22]   Robinson, W.P., Lauzon, J.L., Innes, A.M., Lim, K. and Arsovska, S. (2007) Origin and outcome of pregnancies affected by androgenetic/biparental chimerism. Human Reproduction, 22, 1114-1122. doi:10.1093/humrep/del462

[23]   Hughes, I.A., Nihoul-Fékété, C., Thomas, B. and Cohen- Kettenis, P. (2007) Consequences of the ESPE/LWPES guidelines for diagnosis and treatment of disorders of sex development. Best Practice & Research Clinical Endocrinology & Metabolism, 21, 351-365. doi:10.1016/j.beem.2007.06.003

[24]   Looijenga, L.H.J., Hersmus, R., Oosterhuis, J.W., Cools, M. and Drop, S.L.S. (2007) Tumor risk in disorders of sex development (DSD). Best Practice & Research Clinical Endocrinology & Metabolism, 21, 480-495. doi:10.1016/j.beem.2007.05.001

[25]   Cools, M., Drop, S.L.S., Wolffenbuttel, K.P., Oosterhuis, J.W. and Looijenga, L.H.J. (2006) Germ cell tumors in the intersex gonad: Old paths, new directions, moving frontiers. Endocrine reviews, 27, 468-484. doi:10.1210/er.2006-0005

 
 
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