Thirty-two new cases with small supernumerary marker chromosomes detected in connection with fertility problems: Detailed molecular cytogenetic characterization and review of the literature

Abstract

Thirty-two patients with fertility problems were identified as carriers of small supernumerary marker chromosomes (sSMC). Molecular cytogenetic techniques were used to characterize their chromosomal origin. Together with the other cases available in the literature 111 sSMC cases have now been detected in connection with fertility problems in otherwise clinically healthy persons and characterized for their genetic content. According to this study, in 60% of the cases the sSMC originated from chromosomes 14 or 15. Euchromatic imbalances were caused by the sSMC presence in 30% of the cases. Notably, in 53% of infertile sSMC carriers, the sSMC was parentally transmitted. As we found indications of an as yet unknown mechanism for the elimination of sSMC from the human gene pool, sSMC could also play a role in elucidating the process of chromosome gain and loss during evolution. Nonetheless, further detailed molecular analysis will be necessary in the future to characterize the mechanisms and genetic basis for this phenomenon.Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-57505 Originally published at: Manvelyan, Marina; Riegel, Mariluce; Santos, Monica; Fuster, Carme; Pellestor, Franck; Mazaurik, Marie-Luise; Schulze, Bernt; Polityko, Anna; Tittelbach, Hanne; Reising-Ackermann, Gisela; Belitz, Britta; Hehr, Ute; Kelbova, Christina; Volleth, Marianne; Gödde, Elisabeth; Anderson, Jasen; Küpferling, Peter; Köhler, Sigrid; Duba, Hans-Christoph; Dufke, Andreas; Aktas, Dilek; Martin, Thomas; Schreyer, Isolde; Ewers, Elisabeth; Reich, Daniela; Mrasek, Kristin; Weise, Anja; Liehr, Thomas (2008). Thirty-two new cases with small supernumerary marker chromosomes detected in connection with fertility problems: detailed molecular cytogenetic characterization and review of the literature. International Journal of Molecular Medicine, 21(6):705-714.Abstract. Thirty-two patients with fertility problems were identified as carriers of small supernumerary marker chromosomes (sSMC). Molecular cytogenetic techniques were used to characterize their chromosomal origin. Together with the other cases available in the literature 111 sSMC cases have now been detected in connection with fertility problems in otherwise clinically healthy persons and characterized for their genetic content. According to this study, in 60% of the cases the sSMC originated from chromosomes 14 or 15. Euchromatic imbalances were caused by the sSMC presence in 30% of the cases. Notably, in 53% of infertile sSMC carriers, the sSMC was parentally transmitted. As we found indications of an as yet unknown mechanism for the elimination of sSMC from the human gene pool, sSMC could also play a role in elucidating the process of chromosome gain and loss during evolution. Nonetheless, further detailed molecular analysis will be necessary in the future to characterize the mechanisms and genetic basis for this phenomenon.

Case Report A small supernumerary marker chromosome, derived from chromosome 22, possibly associated with repeated spontaneous abortions

“…The mechanism by which sSMCs influence fertility has not yet been understood (Manvelyan et al, 2008). It has been suggested that sSMCs may lead to reduced fertility in males without additional clinical symptoms in connection with the sSMC (Mulcahy and Jenkyn, 1972;Chandley et al, 1975;Mau et al, 1997;Manvelyan et al, 2008).…”

“…It has been suggested that sSMCs may lead to reduced fertility in males without additional clinical symptoms in connection with the sSMC (Mulcahy and Jenkyn, 1972;Chandley et al, 1975;Mau et al, 1997;Manvelyan et al, 2008). According to population studies, sSMCs are found approximately 2.9 times more often in healthy persons with un-explained infertility compared to the general population (Manvelyan et al, 2008). Manvelyan et al (2008) reported that an enhanced rate of repeated abortions in sSMC carriers or their partners was observed in 22-35% of the cases.…”

“…Cytogenetic abnormalities are well established as an important cause of both sporadic and recurrent spontaneous abortions (Blumberg et al, 1982). More than 50% of spontaneous miscarriages carry chromosomal disorders, up to 96% of which are numerical chromosomal abnormalities consisting of the presence of small supernumerary marker chromosomes (sSMCs), sex chromosome aberrations and constitutional aberrations such as inversions and translocations (Diego-Alvarez et al, 2006;Manvelyan et al, 2008). In a recent study, the proportion of individuals having sSMCs in the normal population was reported as 0.044%, while the proportion was as high as 0.125% in infertile groups (Manvelyan et al, 2008).…”

“…Fertility problems and/or infertility are common phenomenons, and their presumptive causes include anatomical, endocrinological and immunological factors, infections, thrombophilic disorders, and other unexplained causes (Diego-Alvarez et al, 2006;Manvelyan et al, 2008). In about 20% of infertile couples, the etiology remains 'unexplained'.…”

“…In about 20% of infertile couples, the etiology remains 'unexplained'. Most, if not all, the aforementioned factors of infertility are likely to have genetic components, such as deleterious gene mutations and microdeletions and the presence of constitutional, numerical and structural aberrations of chromosomes (Manvelyan et al, 2008). Cytogenetic abnormalities are well established as an important cause of both sporadic and recurrent spontaneous abortions (Blumberg et al, 1982).…”