Meiotic segregation study of a novel t(3;6)(q21;q23) in an infertile man using fluorescencein situhybridization (FISH)

Abstract

Male carriers with balanced reciprocal translocations can produce a variable proportion of unbalanced gametes resulting in reproductive failures. The presence of a structural rearrangement may induce an interchromosomal effect. This is characterized by abnormal bivalents not involved in the reorganization thereby yielding non-disjunction, which would present as aneuploid spermatozoa for these chromosomes. In the present case report segregation analysis of the sperm and investigation of interchromosomal effect were carried out using cytogenetic and fluorescence in situ hybridization (FISH) analysis on blood lymphocytes. The karyotype of the patient was 46,XY,t(3;6)(q21;q23). During sperm segregation analysis a total of 2,002 sperms were evaluated, of which 46.8% showed normal/balanced (alternate segregation mode) and 53.2% of sperm showed an abnormal signal pattern. A significant difference in the frequency of the estimated number of chromosome anomalies was observed in the translocation carrier when compared to the normozoospermic group (P<0.0001) and the oligozoospermic group (P<0.0001). Meiotic segregation analysis of sperm together with aneuploidy assessment for X, Y, and 17 chromosomes using FISH allows for the determination of a reproductive prognosis in male balanced translocation carriers and can be used for appropriate genetic counseling.

Interchromosomal effect: Report of a father and son, bearing different translocations of the same chromosome, and a review of the current literature

“…(Machev et al (2005) took 6 translocation carriers under investigation (two reciprocal and four Robertsonian), comparing sperm aneuploidy rates with control groups, and found statistically significant differences. Another study (Mokánszki et al, 2012) looked for ICE by observing the aneuploidy frequencies of chromosomes X, Y and 17, in a t(3;6)(q21;q23) carrier. Since 17th chromosome is rarely investigated, this is another important study.…”

Inheritance of balanced translocation t(17; 22) from a Down syndrome mother to a phenotypically normal daughter

“…Individuals with balanced reciprocal translocations are known to have high rates of unbalanced gametes, to have impaired or reduced gametogenesis, to produce unbalanced embryos at high rates, and to have a greater chance of being infertile and/or a higher risk of conceiving chromosomally abnormal pregnancies that lead to recurrent spontaneous abortions or children with congenital anomalies (Fischer et al, 2010;Fiorentino et al, 2011;Mokánszki et al, 2012). Possible mechanisms whereby such translocations may have a phenotypic effect include cryptic unbalanced rearrangements, uniparental disomy, and disruption of putative genes at the breakpoints, unmasking recessive alleles on the normal homologs (Dufke et al, 2001).…”

Reproductive outcome of a case with familial balanced translocation t(3;6): implications for genetic counseling

“…However, when one member of a couple carries a balanced chromosome translocation, the risk of miscarriage is approximately doubled (Kavalier, 2005). Individuals with balanced reciprocal translocations are known to have high rates of unbalanced gametes, exhibit impaired or reduced gametogenesis, produce large numbers of unbalanced embryos, and have a greater chance of being infertile and/or a high risk of conceiving chromosomally abnormal pregnancies that lead to recurrent spontaneous abortions or children with congenital anomalies (Fischer et al, 2010;Fiorentino et al, 2011;Mokánszki et al, 2012).…”