Parthenogenetic chimaerism/mosaicism with a Silver-Russell syndrome-like phenotype

Abstract

IntroductionWe report a 34-year-old Japanese female with a Silver-Russell syndrome (SRS)-like phenotype and a mosaic Turner syndrome karyotype (45,X/46,XX).Methods/ResultsMolecular studies including methylation analysis of 17 differentially methylated regions (DMRs) on the autosomes and the XIST-DMR on the X chromosome and genome-wide microsatellite analysis for 96 autosomal loci and 30 X chromosomal loci revealed that the 46,XX cell lineage was accompanied by maternal uniparental isodisomy for all chromosomes (upid(AC)mat), whereas the 45,X cell lineage was associated with biparentally derived autosomes and a maternally derived X chromosome. The frequency of the 46,XX upid(AC)mat cells was calculated as 84% in leukocytes, 56% in salivary cells, and 18% in buccal epithelial cells.DiscussionThe results imply that a parthenogenetic activation took place around the time of fertilisation of a sperm missing a sex chromosome, resulting in the generation of the upid(AC)mat 46,XX cell lineage by endoreplication of one blastomere containing a female pronucleus and the 45,X cell lineage by union of male and female pronuclei. It is likely that the extent of overall (epi)genetic aberrations exceeded the threshold level for the development of SRS phenotype, but not for the occurrence of other imprinting disorders or recessive Mendelian disorders.

Zygotes segregate entire parental genomes in distinct blastomere lineages causing cleavage-stage chimerism and mixoploidy

“…6D) into the origin of human parthenogenetic chimeric cases described by Strain et al (1995) and Yamazawa et al (2010) and the androgenetic chimeras reported by Kaiser-Rogers et al (2006) and Makrydimas et al (2002). These human parthenogenetic and androgenetic chimeras developed in the absence of a fertilization error and contained two distinct cell lineages, a biparental and a uniparental maternal or paternal, respectively.…”

“…Parthenogenesis refers to asexual reproduction, whereby offspring results from an unfertilized oocyte undergoing mitotic divisions, and gynogenesis indicates the development of an embryo with only maternal DNA due to activation of the egg by a sperm that does not unite with the egg's nucleus. Although parthenotes/gynogenotes are not viable in humans, several cases of mosaic individuals, exhibiting a mixture of aberrant diploid cells with only maternal DNA and normal diploid biparental cells do exist (Strain et al 1995;Giltay et al 1998;Yamazawa et al 2010;Xia et al 2014). Those individuals are usually ascertained by cytogenetic and molecular marker analysis, as they for instance may be afflicted with disorders of sex development caused by the presence of 46,XX and 46,XY cell lineages.…”

Silver–Russell syndrome in a patient with somatic mosaicism for upd(11)mat identified by buccal cell analysis

“…2C, Supplementary Table SII). We further performed microsatellite analysis for multiple loci on various chromosomes using leukocyte and buccal cell genomic DNA samples of this patient and leukocyte genomic DNA samples of the parents, thereby excluding genome wide uniparental maternal isodisomy as an extremely rare condition for SRS [Yamazawa et al, 2010] (Supplementary Table SII and Fig. S1).…”

Androgenetic/biparental mosaicism in a girl with Beckwith–Wiedemann syndrome-like and upd(14)pat-like phenotypes

“…We next performed combined bisulfite restriction analysis for multiple DMRs, as reported previously. 13 All the autosomal DMRs exhibited markedly skewed methylation patterns consistent with predominance of paternally inherited clones, whereas the XIST-DMR on the X chromosome showed a normal methylation pattern ( Figure 1a). …”