Double autosomal/gonosomal mosaic aneuploidy: study of nondisjunction in two cases with trisomy of chromosome 8

Abstract

We report cytogenetic and molecular investigations performed in two cases of mosaic trisomy 8 combined with mosaic sex chromosome aneuploidy. In a 35-year-old female, presenting with short stature, gonadal dysgenesis, and a multiple congenital anomalies/mental retardation syndrome typical of trisomy 8, chromosome analysis from peripheral lymphocytes showed the presence of three cell lines, whose karyotypes were 45,X (59.2%), 46,X,+8 (1.2%), and 47,XX,+8 (39.6%), respectively. The same cell lines were found in a skin fibroblast culture, though in different proportions. The second patient, a 9-month-old male with multiple skeletal abnormalities, showed a 47,XY,+8 and a 47,XXY cell line in both peripheral lymphocytes (61.7% and 38.3%, respectively) and skin fibroblasts (92.8% and 7.2%, respectively). To determine the events underlying the origin of these complex karyotypes we performed Southern blot and polymerase chain reaction (PCR) analysis using polymorphic DNA markers from the X chromosome and from chromosome 8. Both supernumerary chromosomes 8, and, in case 2, the two X chromosomes, appeared to be identical, lacking detectable recombination events. We conclude that, in both cases, the most likely mechanism underlying the origin of the mosaic cell lines was formation of a normal zygote, followed by mitotic errors during early divisions.

Origin of nondisjunction in trisomy 8 and trisomy 8 mosaicism

“…29 Studies of trisomy 8 mosaicism in live births have demonstrated 12 cases of mitotic duplication and only one case of probable meiotic origin. 14,25,28,29 Three cases of confined placental mosaicism involving trisomy 8 ascertained through mothers undergoing CVS for advanced maternal age also showed somatic (postmeiotic) origin of the trisomic cell line, 30 as expected in theory. 15 Our results add 20 mitotic cases (including five seemingly nonmosaic cases: two live births, two spontaneous abortions, one CVS) and two maternal meiotic cases (two non-mosaic spontaneous abortions) ( Table 2).…”

“…16,20 Looking only at the mitotic cases in our study, the skewed sex ratio persists (15M:5F). A postzygotic (mitotic) duplication of a chromosome 8 in the early embryo would be expected to occur equally frequently Data from the literature 14,25,[28][29][30] and present study.…”

“…26,27 In order to increase our understanding of the mechanisms underlying chromosomal nondisjunction we have performed a molecular study on 26 cases with trisomy 8 or trisomy 8 mosaicism, for which only a few cases have been studied so far. 14,25,[28][29][30] …”

Trisomy 8 mosaicism in a patient with heterotaxia

“…Tissue-specific mosaicism, as well as the potential for uniparental disomy as a result of trisomy rescue, were invoked as possible explanations (Nucaro et al, 2003). CT8M was found to be mostly due to mitotic nondisjunction error in live-born infants (Robinson et al, 1993;DeBrasi et al, 1995;James and Jacobs, 1996;Seghezzi et al, 1996;Karadima et al, 1998). Meiotic errors were thought to only result in miscarriages (James and Jacobs, 1996;Karadima et al, 1998).…”

Analysis of the Origin of the Extra Chromosome in Trisomy 8 in 4 Cases of Spontaneous Abortions

“…In one molecular study [9], 4 spontaneous abortions showing 100% trisomic cells were all of maternal meiotic origin, while 1 liveborn with apparent nonmosaic trisomy 8 was consistent with a mitotic gain of the extra chromosome. Studies of trisomy 8 mosaicism in liveborns have demonstrated 9 cases of mitotic duplication and only 1 case of meiotic origin [9,28,29]. Three cases of confined placental mosaicism involving trisomy 8 ascertained through mothers undergoing chorionic villus sampling for advanced maternal age also showed somatic (postmeiotic) origin of the trisomic cell line [30], as expected form theoretical considerations [31].…”