Forty-eight new cases with infertility due to balanced chromosomal rearrangements: Detailed molecular cytogenetic analysis of the 90 involved breakpoints

Abstract

Abstract. A molecular cytogenetic study was performed on 48 infertile patients who were identified as carriers of balanced translocations (40 cases), inversions (6 cases) or insertions (2 cases) by means of banding cytogenetics. Cases with a Robertsonian translocation or pericentric inversion 2 or 9 were not included. In summary, 100 break-events occurred in these patients, and 90 different chromosomal regions were involved. Thus, this study confirmed the presence of abnormal karyotypes in a subgroup of patients seeking infertility treatment. Breaks were demonstrated to appear preferentially in GTG-light bands in these patients. Furthermore, the observed breakpoints were associated with genomic regions prone to instability due to the presence of segmental duplications. Nonetheless, further detailed molecular analysis will be necessary in the future to characterize the mechanisms and genetic basis for this phenomenon.

Impaired Spermatogenesis due to Small Supernumerary Marker Chromosomes: The Reason for Infertility Is Only Reliably Ascertainable by Cytogenetics

“…There may be mutations in specific genes, like azoospermia factor ( AZF ) or cystic fibrosis transmembrane conductance regulator ( CFTR ) [Manvelyan et al, 2008;Wosnitzer et al, 2014;Röpke and Tüttelmann, 2017;Colaco and Modi, 2018;Vander Borght and Wyns, 2018]. Still, fertility may be impaired as well by (a) numerical chromosomal alterations, like (mosaic) trisomy or monosomy of (one of) the gonosomes [Mau-Holzmann, 2005;Manvelyan et al, 2007;Wosnitzer et al, 2014;Neto et al, 2016], (b) structural chromosomal abnormalities, like balanced rearrangements (translocations, insertions, inversions or even complex chromosomal rearrangements) [Liehr and Weise, 2007], or (c) a combination of numerical and structural chromosomal alterations, i.e., the presence of a small supernumerary marker chromosome (sSMC) [Manvelyan et al, 2008;Liehr, 2014;Armanet et al, 2015].…”

Balanced reciprocal translocation t(5;13)(q33;q12) and 9q31.1 microduplication in a man suffering from infertility and pollinosis

“…Chromosome 5 participates rarely in reciprocal translocations with reproductive consequences (Manvelyan et al 2007;Stana and Lungeanu 1999;Uchiyama et al 2002) (Table 1). The translocation in our patient involves the breakpoint region 5q33, where, according to the MapViewer Build 37.2, more than 129 genes are located.…”

“…Reciprocal translocations t(5;13) with different breakpoints have been published in six subjects in the literature, whereas only one case was found in an infertile man (Dimova et al 2003;Masuno et al 1991;Rodríguez de Alba et al 1999;Stana and Lungeanu 1999;Uchiyama et al 2002;Yanagisawa et al 1978). But molecular karyotyping shows that one rearrangement is often associated with other chromosomal changes, particularly those involving the loss of one sex chromosome or segmental duplications (Emanuel and Shaikh 2001;Manvelyan et al 2007). The existence of multiple independent structural abnormalities and resulting phenotypes are often more complex than expected.…”

New aspects on chromosomal instability: Chromosomal break-points in Fanconi anemia patients co-localize on the molecular level with fragile sites

“…Due to these findings FS became a novel significance in the field of cancer genetics. Besides cancer, FS play a role in chromosome evolution in hominoidae: there is evidence that evolutionary conserved break-points co-localize with known FS on the molecularcytogenetic level (15). Therefore, FS seem to act as 'hot-spots of recombination'.…”