Volume 12, Issue 8 (8-2014)                   IJRM 2014, 12(8): 581-0 | Back to browse issues page

XML Persian Abstract Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Hasanzadeh-NazarAbadi M, Baghbani F, Namazi I, Mirzaee S. Robertsonian translocation between chromosomes (no.21/14) in relation to the history of spontaneous abortion in a family. IJRM 2014; 12 (8) :581-0
URL: http://ijrm.ir/article-1-570-en.html
1- Department of Medical Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran , nazarabadim@mums.ac.ir
2- Department of Medical Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Full-Text [PDF 266 kb]   (1263 Downloads)     |   Abstract (HTML)  (6601 Views)
Full-Text:   (617 Views)
Introduction
 
Recurrent pregnancy loss (RPL) defined as two or more miscarriages before 20 weeks of gestation, affects up to 15-20% of couples (1, 2). It is proposed that the prevalence of chromosomal abnormalities in spontaneously aborted fetuses is as high as 50% which more than 80% of them occur within the first three months of gestation (3). Several factors are associated with such pregnancies complication, these are including: endocrinology imbalance, immune dysfunction, genetic disorder, advanced maternal age, gravity, body mass index (BMI) BMI >25, BMI <18, genital infectious, environmental toxins, anatomic uterine defects and chromosomal abnormalities (2-6). Although the cause of most habitual miscarriage is unknown nevertheless, parental chromosomal rearrangement is one the possible cause of such recurrent spontaneous abortion (RSA) in the first trimester of gestation (6).
Centric fusion of two acrocentric chromosomes results in robertsonian translocation, which is one of the most common structural rearrangements in humans with an incidence of 1.23 per 1000 live birth. Carriers of robertsonian translocations are phenotypically normal, but they are at high risk of having chromosomally abnormal pregnancies (7). The evidence has been suggested that, the frequency of balanced rearrangement in couples with RSA is 20 fold higher than in the general population (8, 9). In the present study, 10 members of related family with consanguinity marriage (first cousin) with the history of recurrent miscarriage were assessed for cytogenetic disorders searching for balanced chromosomal rearrangement.
 
Case report
 
A family with a history of RPL was referred to the Department of human genetics for cytogenetic evaluation. After obtaining informed consent, 3 ml of peripheral whole blood samples were drawn into sterile heparinized tube so coagulation prevented by additional of heparin. The mononuclear cells are cultured for three days in the presence of RPMI 1640 medium, supplemented with 20% of fetal calf serum, penicillin and streptomycin. The lymphocytes were stimulated by phytohemagglutinin to proliferate. At the end of this period, the culture was treated with colcemid, which disrupts mitotic spindles and prevents complication of mitosis. This greatly enriches the population of metaphase cells. The lymphocytes were harvested and treated briefly with hypotonic solution (0.05 M KCL). This makes the nuclei well osmotically. The swollen cells were fixed (with three part ethanol and one part acetic acid), dropped on to a microscope slide dried. Then, the cells were stained with trypsin-giemsa, in order to induce banding pattern.
Each chromosome was analyzed for its presence and pairing 46 human chromosomes in well-defined order, based on characteristic band. The 23 pairs differ in the length of the arms and each show unique banding pattern. 10 members of related family with consanguinity marriage (first cousin) with the history of recurrent abortion who were phenotypically normal were referred to medical genetics laboratory for cytogenetic analysis searching for balanced chromosomal rearrangement.
The results were indicated that in 6 members of these family appeared with similar balanced robertsonian translocation between chromosomes no.21/14 which 4 member and proband's Karyotype is represented in plate 1-5. Chromosomal constitution appeared with 21q/14q (q21.1, q11.2).



Figure 1. Pedigree of family with robertsonian translocation



Plate 1. A Karyotype of the female with Robertsonian translocation between chromosomes No.21 to No 14
45 XX 21q/14q (q21.1, q11.2). (V-4)



Plate 2. A Karyotype of a male with Robertsonian translocation between chromosomes No.21 to No 14
45 XY 21q/14q (q21.1, q11.2). (V-7)



Plate 3. A Karyotype of a male with Robertsonian translocation between chromosomes No.21 to No 14
45 XY 21q/14q (q21.1, q11.2). (V-8)



Plate 4. A Karyotype of a male with Robertsonian translocation between chromosomes No.21 to No 14
45 XY 21q/14q (q21.1, q11.2). (V-1)



Plate 5. Proband's karyotype with down syndrome, 46, XY, t (21/14). (VI-3)


Discussion
 
Chromosomal rearrangement leads to reduced fertility in both gender. About 15-20% of pregnancies that end in spontaneous abortion occur in the first trimester. It has been reported that, the most common cause of spontaneous abortion in the first trimester (approximately 50%) is chromosomal abnormalities. The majority of chromosomal anomalies (95%) are numerical, about 60% are trisomy’s, 20% are X monosomy and the remainder are (15%) polyploidy especially triploidy (8). On the other hand, half of the structural abnormalities may be inherited from a parents who carrying a balanced chromosomal translocation which are at a higher risk of having children with chromosomal abnormalities (10, 11, 12). It has been reported in some related articles that, the risk of RSA is increased in couples who one of them has such balanced rearrangement (9, 10).
Overall, carriers of balanced rearrangements are at high risk of recurrent spontaneous abortion, althought the phenotype of such couples seem to be normal, but  neverthelese due to the production of unbalanced gametes, recurrent miscarriage or children with abnormal phenotypes might be observed (13, 14). In addition two recent studies show that a higher incidence of chromosomal translocation, directly increases the incidence of abortion in families while any increase in the incidence of chromosome inversion is not associated with an increased miscarriage in couples (13, 15). Cytogenetically, robertsonian translocation or centric fusion of two long arm of acrocentric chromosomes) involving chromosome 21 are the most common structural chromosomal aberrations, which occur with an incidence of ∼1 in 1000 in the general population (16). Although it seems that the prevalence of these structural abnormalities in males and females is similar, but a recent study found that women carrying Robertsonian translocation, carry the abnormality to the fetus four times more than men (16).
In our study 10 members of related family with the history of recurrent abortion were assessed for cytogenetic evaluation. The results were indicated that only 6 member of this family appeared with balanced Robertsonian translocation between chromosomes No.21/14 (plate 1-4). This results are in agreement with several previous studies which claimed that an increased risk of spontaneous abortion in couples with balanced chromosomal rearrangements compared with general population (2).
 
Conclusion
 
Cytogenetic analysis of couples with the history of recurrent abortions should be suggested compulsory to estimate the probable presence of any chromosomal rearrangement. This offer will be valuable information for genetic consulting.
 
Acknowledgments
 
The authors are grateful for financial support provided by Mashhad University of Medical Sciences. In addition, we would like to express our appreciation to Mrs. Rabani and Mrs. Hasanzadeh for their excellent technical assistant.
 

 
Type of Study: Original Article |

References
1. Pal S, Ma SO, Norhasimah M, Suhaida MA, Siti Mariam I, Ankathil R, et al. Chromosomal abnormalities and reproductive outcome in Malaysian couples with miscarriages. Singapore Med J 2009; 50: 1008-1012.
2. Hassanzadeh Nazarabadi M, Raoofian R, Abutorabi R. Balanced Chromosomal Translocations of Parents in Relation to Spontaneous Abortions. J Sci 2005; 16: 203-208.
3. Middeldorp S, Goddijn M. [Recurrent miscarriage and thrombophilia]. Ned Tijdschr Geneeskd 2006; 150: 189-193. (In Dutch)
4. Horne AW, Alexander CL. Recurrent miscarriage. J Fam Plann Reprod Health Care 2005; 31; 103-107. [DOI:10.1783/1471189053629428]
5. Lee RM, Silver RM. Recurrent pregnancy loss: summary and clinical recommendations. Semin Reprod Med 2000; 18: 433-440. [DOI:10.1055/s-2000-13733]
6. Niroumanesh S, Mehdipour P, Farajpour A, Darvish S, et al. A cytogenetic study of couples with repeated spontaneous abortions. Ann Saudi Med 2011; 31: 77-79. [DOI:10.5144/0256-4947.2011.77]
7. Ko DS, Cho JW, Lee HS, Kim JY, Kang IS, Yang KM, et al. Preimplantation genetic diagnosis outcomes and meiotic segregation analysis of robertsonian translocation carriers. Fertil Steril 2013; 99: 1369-1376. [DOI:10.1016/j.fertnstert.2012.12.010]
8. Ananthapur V, Avvari S, Tella S, Nallari P, Akka J. A Robertsonian Translocation rob (14;15) (q10:q10) in a Patient with Recurrent Abortions: A Case Report. J Reprod Infertil 2010; 11: 197-200.
9. Shaffer LG, Spikes AS, Macha M, Dunn R. Identification of a subtle chromosomal translocation in a family with recurrent miscarriages and a child with multiple congenital anomalies. A case report. J Reprod Med 1996; 41: 367-371.
10. Tsui KM, Yu WL, Lo FM, Lam TS. A cytogenetic study of 514 Chinese couples with recurrent spontaneous abortion. Chin Med J (Engl) 1996; 109: 635-638.
11. Ogasawara M, Aoki K, Okada S, Suzumori K. Embryonic karyotype of abortuses in relation to the number of previous miscarriages. Fertil Steril 2000; 73: 300-304. [DOI:10.1016/S0015-0282(99)00495-1]
12. Regan L, Rai R. Epidemiology and the medical causes of miscarriage. Baillieres Best Pract Res Clin Obstet Gynaecol 2000; 14: 839-854. [DOI:10.1053/beog.2000.0123]
13. Ozawa N, Maruyama T, Nagashima T, Ono M, Arase T, Ishimoto H, et al. Pregnancy outcomes of reciprocal translocation carriers who have a history of repeated pregnancy loss. Fertil Steril 2008; 90: 1301-1304. [DOI:10.1016/j.fertnstert.2007.09.051]
14. Sugiura-Ogasawara M, Ozaki Y, Sato T, Suzumori N, Suzumori K. Poor prognosis of recurrent aborters with either maternal or paternal reciprocal translocations. Fertil Steril 2004; 81: 367-373. [DOI:10.1016/j.fertnstert.2003.07.014]
15. De Braekeleer M, Dao TN. Cytogenetic studies in couples experiencing repeated pregnancy losses. Hum Reprod 1990; 5: 519-528. [DOI:10.1093/oxfordjournals.humrep.a137135]
16. Keymolen K, Staessen C, Verpoest W, Michiels A, Bonduelle M, Haentjens P, et al. A proposal for reproductive counselling in carriers of Robertsonian translocations: 10 years of experience with preimplantation genetic diagnosis. Hum Reprod 2009; 24: 2365-2371. [DOI:10.1093/humrep/dep201]

Send email to the article author


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Designed & Developed by : Yektaweb