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Genetic and Clinical Features of Triploid Fetus: A Case Report in Han Chinese Population.

Byline: Jiansheng Zhu, Hui Liu, Yaqun Wang, Muhammad Riaz Khan, Ihtisham Bukhari and Baolong Wang

Abstract

Triploidy is characterized by the presence of an additional set of chromosome in organisms. It has been proved lethal for humans' fetus and causing abortion at last trimester of pregnancy. Some of the triploidy neonates can survive up to several weeks with several physical and mental abnormalities. In current study we enrolled a 27-year-old pregnant woman for genetic counseling with a suspect of Edward's syndrome (trisomy 18) at her gestation period of 16 weeks, GTG-banded metaphase analysis revealed a karyotype of 69 XXX. Microsatellite based genotyping of fetus and parents revealed that triploidy is initiated during meiosis-I and inherited from mother. Therefore, we suggest that the diagnosis of triploidy should be performed at early stage of gestation to avoid the complication at late stages of pregnancy.

Key words: triploidy 69 XXX, digynic triploidy, diandric triploidy, prenatal Diagnosis, fetal diagnosis.

Triploidy syndrome is an extremely rare and lethal chromosomal disturbance in which individuals have 69 rather than 46 chromosomes.

The majority of fetuses with triploidy are spontaneously miscarried during the pregnancy, and some of neonates with triploidy can survive for several hours after the birth with several physical defects like severe growth retardation and other multiple birth defects (Hassold et al., 1980; Redline et al., 1998). Despite the unknown etiology of triploidy, various studies have shown a possible maternal and paternal genetic factors contributing to the recurrent triploid pregnancies (Brancati et al., 2003; Pergament et al., 2000; Check et al., 2009). Keeping in view all these possible risk factors, we initiated this study to evaluate the possible abnormalities and genetic background of aborted triploid fetus reported in Chinese Han population.

Patient and clinical findings

In current study a 27-year-old pregnant woman was referred for genetic counseling of abnormal maternal serum screening test at her gestation age of 16 weeks, screening tests were positive for Edward's syndrome (trisomy 18) with very low chorionic gonadotropin and normal alpha- fetoprotein levels (Table I). Several other serological tests were performed which revealed low level of creatinine, blood urea nitrogen and alkaline phosphates. Serum high density lipoprotein (HDL) level was little bit elevated (Table II). The other serological parameters were found normal in patient. The calculated risk for trisomy 18 was more than 1:10; amniotic fluid gradually reduced from gestation age of 14 to 20 weeks, and an ultrasound examination revealed severe oligohydramnios.

Table I.- Biochemical findings at second trimester of pregnancy.

Maternal###Concentration###Multiple###Reference

Serum###of median

Markers

Alpha-###58.40 U/ml###1.44###0.40~2.50

fetoprotein

Human###1.12 ng/ml###0.06###0.25~2.50

chorionic

onadotropin

Amniocentesis was performed at 21st week of pregnancy and the amniotic fluid was used to examine karyotype and genotype of the fetus. GTG- banded metaphase analysis revealed 69 XXX karyotype of fetus (Fig.1A), while parents have normal karyotype. To find out the inheritance pattern and exact cause of triploidy in fetus; a set of meiosis specific microsatellite markers was used (Table III). The molecular analysis of fetus and parents revealed that the extra haploid set of chromosome in fetus is resulted from nondisjunction at maternal meiosis-I. After detailed counseling and personal decision of the patient, the pregnancy was terminated at 25th week of gestation.

Table II.- Serological examination of mother at second trimester of pregnancy.

Biochemical Markers###Results###Reference###Unit

###Value

Creatinine (Cr )###37.13###50.00~120.00###mol/L

Blood urea nitrogen###1.58###2.14~7.14###mmol/L

(BUN)

Alkaline phosphates###32.19###42.00~140.00###IU/L

(ALP)

High density###2.74###0.90~2.30###mmol/L

lipoprotein (HDL)

Table III.- Meiosis specific microsatellite markers used for genotype analysis of fetus and parents.

Markers###Father###Mother###Fetus###Interpretation

D8S1179###12/13###11/13###11/12/13

D21S11###29/31###30/32.2###29/30/32.2###Mat MI

D7S820###8/8###9/12###8/9/12###Mat MI

CSF1PO###12/12###10/10###10/12

D3S1358###15/16###15/17###15/17

D5S818###10/13###11/12###10/11

D13S317###9/12###8/11###8/9/11###Mat MI

D16S539###12/12###9/9###9/12

D2S1338###20/24###20/24###20/24

D19S433###13/14###14.2/15###14/14.2/15###Mat MI

VWA###16/18###17/20###17/18/20###Mat MI

D12S391###17/23###18/19###18/19/23###Mat MI

D18S51###13/16###13/16###13/16

D6S1043###13/18###17/19###17/18/19###Mat MI

FGA###21/23###21/22###21/22

The pathological examinations revealed a female fetus, weight 370g, length 25cm, including intrauterine growth retardation, hypotonia, low-set ears, wide-set eyes (hypertelorism), and limb abnormalities (Fig.1B). Following several physical abnormalities were found in fetus; the left hand had bilateral overlapping of the third and fourth fingers,right hand had bilateral overlapping of second and third fingers, total syndactily of the feet, heart defects, with aplasia of the lungs. The fetus had a small but almost normal appearance of placenta, weight 20g, and size 10cmA-8cm A- 0.7 cm, with two umbilical arteries and one vessel.

Discussion

Triploidy is one of the most common chromosomal aberrations which causes abnormal fetus leading to spontaneous abortion, only rare triploid fetus can live after birth. Although the etiology of triploidy is not clear, the mechanisms of Triploidy may be maternal (digynic triploids) or paternal (diandric triploids). Digynic triploids results from error in first meiosis in oocytes; the resultant fetus has two sets of maternal chromosomes and a single set of paternal chromosomes. Digynic pregnancies usually have a small placenta which secretes less human chorionic gonadotrophin (hCG), and fetal adrenal growth occurs under the influence of hCG, diagynic fetus usually has severe growth retardation associated with marked adrenal hypoplasia (Eidben et al., 1996; McFadden et al., 2002). Diagynic fetus can live upto second trimester, and some can survive few hours after the birth.

Here we enrolled a pregnant woman with diagynic fetus and very low level of gonadotropin; fetus was aborted at 25th week of gestation. A very low level of maternal gonadotropin has been associated with Triplody (Schmidt et al., 1994) and low chorionic gonadotropin and alpha-fetoprotein have also been reported in Down syndrome and trisomy 18 (Lehavi et al., 2005; Ozturk et al., 1990). Therefore, we suggest that the low level of gonadotropin can also be used as a biomarker for triploidy suspect during the second trimester of pregnancy in routine diagnosis.

Morphological analyses of the fetus represent complete abnormal body structure with incomplete growth of body parts and high power lens microscopic examination revealed an abnormal and incomplete internal body structure. Placenta and fetal membranes are appeared to be normal; umbilical cord contains two umbilical arteries and one vessel; these findings are consistent with previous reports (Hassold et al., 1980; Redline et al., 1998).

Unlike other aneuploidies, maternal age is not a risk factor for triploidy. Till now it has not been found any remarkable risk factors of triploidy pregnancies; therefore it indicates that a woman who has had one triploid pregnancy is not susceptible to carry another triploidy fetus. Although triploidy occurs randomly, few women may have recurrent miscarriages due to triploid fetus (Zaragoza et al., 2000; Huang et al., 2004). It has been identified that the maternal susceptibility locus on chromosome 19 is responsible for recurrent hydatidiform moles (Moglabey et al., 1999).

In previous report total 13 embryos in IVF procedure were resulted in two additional triploid embryos, with an overall number of four triploid conceptuses in a woman, authors suggested that the event of triploidy occurred during maternal meiosis II (Pergament et al., 2000). Huang et al. (2002) also reported triploid pregnancy with maternal origin; they speculated that the triploidy may be associated with the errors in both meiosis I and II.

In our present case, a total of 15 markers for 13 different chromosomes were used to analyze the origin of the extra-haploid chromosome. Seven markers revealed that the fetus inherited with two maternal alleles and one paternal allele, which prove maternal inheritance of triploidy that occurred due to failure of homologous chromosome or sister chromatids to separate properly in meiosis-I. More comprehensive studies are required to investigate the possible risk factors and exact underlying mechanism of triploidy occurrence. Therefore, we highly recommend that maternal diagnosis for triploidy must be done at early embryonic stage to avoid the complication of the pregnancy at late stage and to ensure the mothers' health during abortion.

Conflict of interest

All authors have declared that they have no conflict of interest.

Acknowledgements

We would like to thank Yong Zai for technical assistance during data collection and Dr. Jilong Shen, Provincial Laboratory of Zoonoses, Anhui, China, for technical review of this manuscript.

References

Brancati, F., Mingarelli, R. and Dallapiccola, B., 2003. Eur. J. Hum. Genet., 11: 972974.

Check, J.H., Katsoff, B., Summers-Chase, D. and Breitbart, J., 2009. Clin. exp. Obstet. Gynecol., 36:133-134.

Eiben, B., Hammans, W. and Goebel, R., 1996. Prenat. Diagn., 16:377378.

Hassold, T., Chen, N., Funkhouser, J., Jooss, T., Manuel, B., Matsuura, J., Matsuyama, A., Wilson, C., Yamane, J.A. and Jacobs, P.A., 19980. Annls. Hum. Genet., 44: 151 178.

Huang, B., Prensky, l., Thangavelu, M. and Wang, S., 2002.Am. J. Hum. Genet., 71 (Suppl): Abstract 2283.

Huang, B., Prensky, L., Thangavelu, M., Main, D. and Wang, S., 2004. Eur. J. Hum. Genet., 12: 985986.

Lehavi, O., Aizenstein, O., Evans, M.I. and Yaron, Y., 2005.Fetal Diagn. Ther., 20:235-8.

Mcfadden, D. E., Hulait, G., Lockitch, G. and Langlois, S.,2002. Prenat. Diagn., 22:11131114.

Moglabey, Y.B., Kircheisen, R., Seoud, M. E., Mogharbel, N., Van-den., Veyver, I. and Slim, R., 1999. Hum. mol. Genet., 8: 667671.

Ozturk, M., Milunsky, A., Brambati, B., Sachs, E.S., Miller, S.L. and Wands, J.R., 1990. Am. J. med. Genet., 36:480-3.

Pergament, E., Confino, E., Zhang, J.X., Roscetti, L., Xien- chen, P. and Wellman, D., 2000. Prenat. Diagn., 20: 561563.

Redline, R.W., Hassold, T. and Zaragoza, M.V., 1998. Hum. Pathol., 29:505511.

Schmidt, D., Shaffer, L.G., Mccaskill, C., Rose, E. and Greenberg, F., 1994. Am. J. Obstet. Gynecol., 170:77- 80.

Zaragoza, M.V., Surti, U., Redline, R.W., Millie, E. and Chakravarti, A., 2000. Am. J. Hum. Genet., 66: 1807 1820.
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Article Details
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Author:Zhu, Jiansheng; Liu, Hui; Wang, Yaqun; Khan, Muhammad Riaz; Bukhari, Ihtisham; Wang, Baolong
Publication:Pakistan Journal of Zoology
Article Type:Case study
Geographic Code:9CHIN
Date:Apr 30, 2015
Words:1723
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