Small supernumerary marker chromosomes (SMCs) are present in about 0.05% of the human population. In approximately 30% of SMC carriers (excluding the approximately 60% SMC derived from one of the acrocentric chromosomes), an abnormal phenotype is observed. The clinical outcome of an SMC is difficult to predict as they can have different phenotypic consequences because of (1). differences in euchromatic DNA-content, (2). different degrees of mosaicism, and/or (3). uniparental disomy (UPD) of the chromosomes homologous to the SMC. Here, we present 35 SMCs, which are derived from all human chromosomes, apart from chromosome 6, as demonstrated by the appropriate molecular cytogenetic approaches, such as centromere-specific multicolor fluoresence in situ hybridization (cenM-FISH), multicolor banding (MCB), and subcentromere-specific multicolor FISH (subcenM-FISH). In nine cases without an aberrant phenotype, neither partial proximal trisomies nor UPD could be detected. Abnormal clinical findings, such as psychomotoric retardation and/or craniofacial dysmorphisms, were associated with seven of the cases in which subcentromeric single-copy probes were proven to be present in three copies. Conversely, in eight cases with a normal phenotype, proximal euchromatic material was detected as partial trisomy. UPD was studied in 12 cases and subsequently detected in two of the cases with SMC (partial UPD 4p and maternal UPD 22 in a der(22)-syndrome patient), indicating that SMC carriers have an enhanced risk for UPD. At present, small proximal trisomies of 1p, 1q, 2p, 6p, 6q, 7q, 9p, and 12q seem to lead to clinical manifestations, whereas partial proximal trisomies of 2q, 3p, 3q, 5q, 7p, 8p, 17p, and 18p may not be associated with significant clinical symptoms. With respect to clinical outcome, a classification of SMCs is proposed that considers molecular genetic and molecular cytogenetic characteristics as demonstrated by presently available methods.
Deletions of chromosome bands 13q33-34 are rare. Patients with such deletions have mental retardation, microcephaly, and distinct facial features. Male patients frequently also have genital malformations. We report on four patients with three overlapping deletions of 13q33-34 that have been characterized by tiling-path array-CGH. Patient 1 had mental retardation and microcephaly with an interstitial 4.7 Mb deletion and a translocation t(12;13)(q13.3;q32.3). His mother (Patient 2), who also had mental retardation and microcephaly, carried the identical chromosome aberration. Patient 3 was a girl with a de novo insertion ins(7;13)(p15.1;q22q31) and interstitial 4.5 Mb deletion in 13q33-34. She had mental retardation and microcephaly. Patient 4 was a newborn boy with severe genital malformation (penoscrotal transposition and hypospadias) and microcephaly. He had a de novo ring chromosome 13 lacking the terminal 9.3 Mb of 13q. Karyotype-phenotype comparisons of these and eight previously published del13q33-34 patients suggest EFNB2 as a candidate gene for genital malformations in males. Molecular cytogenetic definition of a common deleted region in all patients suggests ARHGEF7 as a candidate gene for mental retardation and microcephaly.
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.
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.
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