Functional disomies of the X chromosome influence the cell selection and hence the X inactivation pattern in females with balanced X‐autosome translocations: A review of 122 cases

Abstract

We reviewed 122 cases of balanced X-autosome translocations in females, with respect to the X inactivation pattern, the position of the X break point and the resulting phenotype. In 77% of the patients the translocated X chromosome was early replicating in all cells analysed. The break points in these cases were distributed all along the X chromosome. Most of these patients were either phenotypically normal or had gonadal dysgenesis, some had single gene disorders, and less than 9% had multiple congenital anomalies and/or mental retardation. In the remaining 23% of the cases the translocated X chromosome was late replicating in a proportion of cells. In these cells only one of the translocation products was reported to replicate late, while the remaining portion of the X chromosome showed the same replication pattern as the homologous part of the active, structurally normal X chromosome. The analysis of DNA methylation in one of these cases confirmed noninactivation of the translocated segment. Consequently, these cells were functionally disomic for a part of the X chromosome. The presence of disomic cells was highly prevalent in translocations with break points at Xp22 and Xq28, even though spreading of X inactivation onto the adjacent autosomal segment was noted in most of these cases. This suggests that selection against cells with a late replicating translocated X is driven predominantly by a functional disomy X, and that the efficiency of this process depends primarily on the position of the X break point, and hence the size of the noninactivated region.(ABSTRACT TRUNCATED AT 250 WORDS)

Heterotaxy and cardiac defect in a girl with chromosome translocation t(X;1)(q26;p13.1) and involvement of ZIC3

“…10,11 This was also the case in the foetus reported by Fritz et al 7 Skewed X-inactivation was also present in our patient, thus mimicking the situation in hemizygous males (functional nullisomy). The specific phenotype of our patient is very likely caused by the absence of functional ZIC3, probably owing to disruption of the transcriptional unit from a regulatory element or owing to a position effect associated with the translocation breakpoints.…”

Are some chromosomes particularly good at sex? Insights from amniotes

“…Indeed, dosage compensation is only partial and gene-specific in birds, and also in platypus (Deakin et al 2008;Itoh et al 2010). In contrast, failure to inactivate the mammal X chromosome or duplications of even small regions on the active X have severe phenotypes (Migeon et al 2000;Schmidt and Du Sart 1992).…”

Disruption ofHDXgene in premature ovarian failure

“…Second, translocation of regulatory domains to another position on the genome might cause alternations in transcriptional regulation due to 'position effect' [Persani et al 2009]. Lastly, in female balanced X;autosome translocations carriers, the normal X chromosome is usually inactivated allowing full expression of genes on the translocated segments [ Schmidt and Du Sart 1992;Yang et al 2011]. Female balanced X; autosome translocation carriers are generally phenotypically normal because the normal X chromosome is completely inactivated in these patients as a result of phenotypic plasticity to prevent deleterious monosomy.…”