Indian Journal of Human Genetics
Home Current Issue Archives Guidelines Subscriptions e-Alerts Login 
Users online: 10
Print this page  Email this page Small font sizeDefault font sizeIncrease font size


 
            Table of Contents  
CASE REPORT
Year : 2012  |  Volume : 18  |  Issue : 2  |  Page : 250-253
 

Genetic counseling in carriers of reciprocal translocations involving two autosomes


1 Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
2 Department of Molecular Medicine and Genetic, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
3 Department of Gynecology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
4 Genetic Lab., Sh. Beheshti Hospital, Hamadan, Iran

Date of Web Publication8-Sep-2012

Correspondence Address:
Hamid Pour-Jafari
Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran, PO Box 518, Hamadan
Iran
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-6866.100802

Get Permissions

 

   Abstract 

One of the main genetic causes involve in the pathogenesis of recurrent abortion is parental chromosomal abnormalities. The central concept in genetic counseling with such families is to estimate the probability of recurrence of unfavorable pregnancy outcomes. The main questions that consultants usually ask are: Why did this happen? What is the risk to be done again?
Our cases were two families with repeated miscarriage. The pedigrees were drawn, the chromosomes of couples were studied, and estimation for recurrent risk was done. We tried to answer those two main questions and clear the results for them.
Parental chromosome abnormalities were founded after karyotyping with GTG technique at 450 band resolution, revealing 46 chromosomes with balanced translocation of autosomes in one of the partner in both families. Recurrent risk was estimated as "high" for their future pregnancies in each family.
Couples in which one partner is the carrier of such balanced translocation have increased risks of infertility, recurrent abortion, and delivery of chromosomally abnormal offspring. Genetic counseling of such couples, therefore, presents a unique challenge and should be considered in dealing with such families.


Keywords: Abortion, family planning, genetic counseling, reciprocal translocation, repeated miscarriages


How to cite this article:
Pourjafari B, Pour-Jafari H, Farimani M, Ghahramani S, Saleh EK. Genetic counseling in carriers of reciprocal translocations involving two autosomes. Indian J Hum Genet 2012;18:250-3

How to cite this URL:
Pourjafari B, Pour-Jafari H, Farimani M, Ghahramani S, Saleh EK. Genetic counseling in carriers of reciprocal translocations involving two autosomes. Indian J Hum Genet [serial online] 2012 [cited 2016 Jun 1];18:250-3. Available from: http://www.ijhg.com/text.asp?2012/18/2/250/100802



   Introduction Top


The presence of chromosome abnormalities in couples with repeated spontaneous abortion is known even if the phenomenon is far from a complete assessment. [1] Patients carrying balanced reciprocal translocation are subject to meiosis nondisjunction risk. Indeed, the mispairing of translocated chromosomes during the first meiotic division can give rise to different forms of segregation, which can result in aneuploidy of the translocated chromosomes. [2] A compilation of the cytogenetic results taken from 79 published surveys of couples with two or more pregnancy losses (comprising 8208 women and 7834 men) showed an overall prevalence of major chromosome abnormalities of 2.9%. This is five to six times higher than that of the general adult population. [3] Results of different studies have shown that chromosomal reciprocal translocations in one of the partners will cause majorities of unfavorable pregnancy outcomes. [4],[5],[6],[7]

The main question that usually genetic counselors should answer to their consultants is to estimate the probability of recurrence of unfavorable pregnancy outcomes (abortion, stillbirth, and birth of malformed child) among their future pregnancies. In case of chromosomal translocations, estimates are made on basis of segregation analyses in actual pedigree. If we have a few of pedigree members,then risk estimate should be performed on basis of our combined data and empiric data from literature. [8] Families with balanced chromosomal changes ascertained by unbalanced progeny, miscarriages, or by chance are interested in their probability for unbalanced offspring and other unfavorable pregnancy outcomes. This is usually done based on the original data published by Stengel-Rutkowski et al.(1988), several decades ago. [9]

Different risks are estimated for unbalanced offspring at birth or at second trimester prenatal diagnosis for abortions or stillbirths/early deaths. These risk estimates varied considerably from translocation to translocation. Here, we present two different family in which one of the partners were carriers of balanced translocation.


   Case Report Top


Our cases were two families living in Hamadan as described below. They were referred to our clinic because of their repeated spontaneous abortion:

  1. Family number I: Female partner was 26 and male partner was 32 years old. They had consanguineous marriage (first cousin). Their medical history has showed four miscarriages during the first trimester of pregnancies. [Figure 1] shows their pedigree chart. As it can be seen, the male partner had two siblings who died at the first month after birth. His karyotype with GTG banding technique showed that he was a balanced carrier of reciprocal translocation between two autosomes, numbers 2 and 12 [Figure 2]. The results of his karyotype was 46, XY, t(2;12)(p21;q22). The karyotyping of his wife showed that she was 45, XX (normal female karyotype). [Figure 2] shows the photographs of normal and translocated chromosomes numbers 2 and 12, displaying also schematic representation of the breakpoint positions.
  2. Family number II: Female partner was 38 and male partner was 50 years old at the time of our study. They had a non-consanguineous marriage. Their medical history has showed two miscarriages during the first trimester of pregnancies. [Figure 3] shows their pedigree chart. As it can be seen, the female partner had mother with three abortions in her medical history. His karyotype with GTG banding technique showed that he was a balanced carrier of reciprocal translocation between two autosomes, numbers 1 and 12 [Figure 3]. The results of her karyotype was 46, XX, t(1;12)(p31;q13). The karyotyping of her husband showed that he was 45, XY (normal male karyotype). [Figure 4] shows the normal and translocated chromosomes numbers 1 and 12, and also it representsschematic diagrams of the breakpoint positions.
Figure 1: Pedigree chart of Family number I, see text for details

Click here to view
Figure 2: Photographs of normal and translocated chromosomes numbers 2 and 12, displaying also
schematic representation of the breakpoint positions


Click here to view
Figure 3: Pedigree chart of Family number II, see text for details

Click here to view
Figure 4: Photographs of normal and translocated chromosomes numbers 1 and 12, displaying also
schematic representation of the breakpoint positions


Click here to view



   Discussion Top


The estimation of the occurrence probability for individual carriers of two different autosome-autosome translocations with breakpoints at different positions is usually done based on the original data published by Stengel-Rutkowski et al.(1988) several decades ago. That data set has never been updated. [9]

For example, probability rates of unbalanced progeny at birth and at second trimester of prenatal diagnosis as well as of unkaryotyped miscarriages and stillbirth/early death of newborn for RCT carriers related to the total number of pregnancies after ascertainment correction are calculated according to the method of Stengel-Rutkowski et al.[10] The ascertainment correction according to Stene and Stengel-Rutkowski [11] is performed by elimination of probands (or index sibships) and carriers with the proband in direct line of descent. The probability rate estimates for unfavorable pregnancies are presented as:



p, risk value; a, number of unfavorable pregnancies after ascertainment correction; n, number of all pregnancies after ascertainment correction; and S, standard deviation.

If the number of abnormal pregnancies after ascertainment correction be 0, the maximal risk estimate m, corresponding to the upper limit of the risk interval, is calculated using the formula:



m, maximal risk where e=2.71828 is the base number for natural logarithms.

It is clear that the larger pedigrees result in accurate estimations. Also, using such formula in clinics takes a lot of time and usually the patients feel that the counselors are doing a lot for noting!

The families usually do not care about such estimations; they want know why those miscarriages, stillbirths/early deaths happened; are they in a high risk for those bad experiences or not? And finally, if the answer is "yes," they are eager to know the genetic counselor's views about those complex estimations. In another word, they want to hear if there is a high, moderate, or low risk for unfavorable pregnancy outcome in a RCT carrier. So, perhaps if the genetic counselors try to adopt their estimations to the roles of segregation during miosis and gametogenesis in carriers of balanced reciprocal translocations, [12] the patients will get a better idea to reach to a final decision. Based on the segregation role, the risk of unfavorable outcomes, in such situations, as we saw in our cases, are high (about one-sixth) and we advised for PGD or prenatal diagnosis.

In addition of those two questions that are the cores of genetic counseling from the patients' side and so genetic counselors might answer and explain them in an comprehensible way, there are two more points that although are in a limited probability, geneticists should bring them to light and pay enough attention. Firstly, the people that are balanced carrier of, at least, some kinds of reciprocal translocation are at a higher risk for malignancy. [13],[14],[15],[16] Therefore, carriers of such translocations should be noticed to have routine check-up for early detection of malignancies. Secondarily, sometimes RCTs lead to abnormalities in other chromosomes, phenomenon called inter-chromosomal effect (ICE); [17],[18] so the risk of unfavorable outcomes in future pregnancies of such individuals may be more than primary estimations. Because matters such as what we mentioned recently are studies called the sensitive studies, [19],[20],[21] talking about them must be with special attention.

 
   References Top

1.Mameli M, Cardia S, Milia A, Aste A, Santucci S, Genazzani AR. Cytogenetic study in 50 couples with recurrent abortions. Gynecol Obstet Invest 1984;17:84-8.  Back to cited text no. 1
    
2.Machev N, Gosset P, Warter S, Treger M, Schillinger M, Viville S. Fluorescence in situ hybridization sperm analysis of six translocation carriers provides evidence of an interchromosomal effect. Fertil Steril 2005;84:365-73.  Back to cited text no. 2
[PUBMED]    
3.Tharapel AT, Tharapel SA, Bannerman RM.Recurrent pregnancy losses and parental chromosome abnormalities: Areview. Br J Obstet Gynaecol 1985;92:899-914.  Back to cited text no. 3
[PUBMED]    
4.Midro AT, Wiland E, Panasiuk B, Le?niewicz R, Kurpisz M. Risk evaluation of carriers with chromosome reciprocal translocation t(7;13)(q34;q13) and concomitant meiotic segregation analyzed by FISH on ejaculated spermatozoa. Am J Med Genet A 2006;140:245-56.  Back to cited text no. 4
[PUBMED]    
5.Kovacheva K, Ahgelova L, Simeonova M, Tsankova G, Ionov M, Khristova V, et al. [Active screening for genetic pathology in newborns. I. Registration of congenital abnormalities]. Akush Ginekol (Sofiia) 2004;43:18-22.  Back to cited text no. 5
    
6.Cammarata M, Corsello G, Marino M, Morabito M, Pecoraro MR, Piccione M, et al. Genetic factors of recurrent abortions. Acta Eur Fertil 1989;20:367-70.  Back to cited text no. 6
[PUBMED]    
7.Sachs ES, Jahoda MG, Van Hemel JO, Hoogeboom AJ, Sandkuyl LA. Chromosome studies of 500 couples with two or more abortions. Obstet Gynecol 1985;65:375-8.  Back to cited text no. 7
[PUBMED]    
8.Stasiewicz-Jarocka B, Raczkiewicz B, Kowalczyk D, Zawada M, Midro AT. [Genetic risk of families with t(1;2)(q42;q33) GTG, RHG, QFQ, FISH]. Ginekol Pol 2000;71:1262-72.  Back to cited text no. 8
[PUBMED]    
9.Stasiewicz-Jarocka B, Haus O, Van Assche E, Kostyk E, Constantinou M, Ryba³ko A,et al. Genetic counseling in carriers of reciprocal chromosomal translocations involving long arm of chromosome 16. Clin Genet 2004;66:189-207.  Back to cited text no. 9
    
10.Stengel-Rutkowski S, Stene S, Gallano P. Risk estimates in balanced parental reciprocal translocations. Monographie des Annales de Genetique, Expansion Scientifique Francaise; 1988.  Back to cited text no. 10
    
11.Stene J, Stengel-Rutkowski S. Genetic risks of familial reciprocal and robertsonian translocation carriers.Cytogenetics of Mammalian Autosomal Rearrangements.In: Daniel A, ed.Alan R. Liss Inc.: New York; 1988. pp. 1-54.  Back to cited text no. 11
    
12.Nussbaum RL, McInnes RR, Willard HF. Thompson and Thompson Genetics in Medicine. 6th ed. Philadelphia, PA: Saunders; 2004: p148   Back to cited text no. 12
    
13.Sheth FJ, Sheth JJ, Verhest A. A three way complex translocation (4; 9; 22) in two patients with chronic myelocytic leukemia. J Cancer Res Ther 2005;1:108-10.  Back to cited text no. 13
[PUBMED]    
14.Liu X, Adams AL. Mucoepidermoid carcinoma of the bronchus: Areview. Arch Pathol Lab Med 2007;131:1400-4.  Back to cited text no. 14
[PUBMED]    
15.McArthur G. Dermatofibrosarcomaprotuberans: Recent clinical progress. Ann Surg Oncol 2007;14:2876-86.  Back to cited text no. 15
[PUBMED]    
16.Rosenhahn J, Weise A, Michel S, Hennig K, Hartmann I, Schiefner J, et al. Cytogenetic characterisation and proteomic profiling of the Imatinib-resistant cell line KCL22-R. Int J Oncol 2007;31:121-8.  Back to cited text no. 16
[PUBMED]    
17.Douet-Guilbert N, Bris MJ, Amice V, Marchetti C, Deloble B, Amice J,et al. Interchromosomal effect in sperm of males with translocations: Report of 6 cases and review of the literature. Int J Androl 2005;28:372-9.  Back to cited text no. 17
    
18.Estop AM, Cieply K, Munne S, Surti U, Wakim A, Feingold E. Is there an interchromosomal effect in reciprocal translocation carriers? Sperm FISH studies. Hum Genet 2000;106:517-24.  Back to cited text no. 18
    
19.Small R, Yelland J, Lumley J, Rice PL. Cross-cultural research: Trying to do it better. 1. Issues in study design. Aust N Z J Public Health 1999;23:385-9.  Back to cited text no. 19
    
20.Wacheck V. Strategies for designing clinical trials for oligonucleotide therapeutics. Drug Discov Today 2004;9:918-23.  Back to cited text no. 20
[PUBMED]    
21.Andersen JS. Clinical trial designs--made to order. J Biopharm Stat 1996;6:515-22.  Back to cited text no. 21
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

Top
Print this article  Email this article
           

    

 
   Search
 
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Article in PDF (235 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
   Introduction
   Case Report
   Discussion
    References
    Article Figures

 Article Access Statistics
    Viewed2963    
    Printed68    
    Emailed4    
    PDF Downloaded49    
    Comments [Add]    

Recommend this journal