Origin and mechanism of formation of 45,X/47,XX,+21 mosaicism in a fetus

Abstract

Chromosome analysis of amniotic fluid cells from a 17-week-old fetus with a nuchal cystic hygroma showed a 45,X/47,XX,+21 karyotype. Analyses of cord blood lymphocytes, skin fibroblasts, amniotic membrane, and chorionic villi demonstrated both cell lines in various proportions. We studied the origin and mechanism of formation of the double mosaic aneuploid using Q-banded chromosomal heteromorphisms, and one RFLP, two VNTRs, one tetranucleotide repeat, 28 CA repeat markers, mapped to every member of chromosomes. The heteromorphic markers examined showed no discordant patterns in parent-to-child transmission or between the two cell lines except for those in chromosomes 21 and X. Fetal DNA was extracted from its established monoclonal fibroblast cell lines with 45,X or 47,XX,+21 karyotypes. Genotyping with the DNA markers showed that each cell line was identical at every locus, except for chromosome 21 or X loci, indicating that the fetus was not a chimera but a mosaic. The 21-trisomic cells had one paternal allele and two maternal heterozygous alleles at the D21S270 locus, and the 45,X (21-disomic) cells had two biparental alleles. Alleles at two X chromosomal loci, DXS991 and DXS8057, were biparental in the 47,XX,+21 cells, whereas only the paternal allele was retained in the 45,X cells. Based on these findings, we concluded that the fetus started as a 47,XX,+21 zygote that had resulted from nondisjunction at the maternal first meiotic division and that one each of the maternally derived chromosomes 21 and X was lost during an early mitotic division, leading to the mosaicism.

Cytogenetic Profiles of 1213 Children with Down Syndrome in South Region of Turkey

“…In our study, the frequency of inv (9) in DS patients was observed to be 1.1%. Pericentric inversion of chromosome 9 is the most common reciprocal translocation in the general population and the prevalence of inv(9) varies with ethnicity.…”

“…This inversion is usually considered as a polymorphism, and its clinical consequences remain unclear [17]. However, inv (9) has been found to be associated with infertility, repeated fetal loss, congenital anomalies and MR, possibly as a predisposing factor for non-disjunction and inter-chromosomal effect [30]. This may indicate that the effect of inv(9) on the development of MR would not be major one, but it may be a riskincreasing factor.…”

“…Constitutional mosaicism consisting of sex chromosome aneuploidy and autosomal trisomy is a rare finding. Most of the reported cases involve X monosomy and trisomy 21 [9] but only a few reports exist with the mosaic DS and Y chromosome abnormality [10]. In this report we present the frequencies and distributions of the postnatal prevalence of CAs in children and newborns with DS physical features, and the relation between the karyotypes and phenotypes in a large group of cases in South Region of Turkey.…”

Sporadic aneuploidy in PHA-stimulated lymphocytes of Turner’s syndrome patients

“…In some of the cases, haplotype analyses suggested a normal zygote formation followed by several mitotic errors during early divisions, resulting in mixoploidy of 45,X/ 46,XX/47, XX+8 (DeBrasi et al 1995). In other cases a meiotic division error of autosomal chromosome was followed by mitotic X chromosome loss, as was seen in patients with 45,X/47,XX+18 (Schubert et al 2002) and 45,X/47,XX,+21 (Harada et al 1998).…”

Pigmentary mosaicism following the lines of Blaschko in a girl with a double aneuploidy mosaicism: (47,XX,+7/45,X)

“…The combination of monosomy X with [Cohen and Davidson, 1972;Schinzel et al, 1974;Hustinx et al, 1974;Prieur et al, 1972Prieur et al, , 1976Serville et al, 1977;Knudtzon et al, 1988;Eiben et al, 1989;Schofield et al, 1992;Franceschini et al, 1996;Mielke et al, 1997;Harada et al, 1998;Genuardi et al, 1999;Schubert et al, 2002;Cogulu et al, 2002], but the combination with trisomy 7 has not. Clinical findings in these patients are summarized in Table II.…”