Spread of X‐chromosome inactivation into autosomal regions in patients with unbalanced X‐autosome translocations and its phenotypic effects

Abstract

Patients with unbalanced X-autosome translocations are rare and usually present a skewed X-chromosome inactivation (XCI) pattern, with the derivative chromosome being preferentially inactivated, and with a possible spread of XCI into the autosomal regions attached to it, which can inactivate autosomal genes and affect the patients' phenotype. We describe three patients carrying different unbalanced X-autosome translocations, confirmed by G-banding karyotype and array techniques. We analyzed their XCI pattern and inactivation spread into autosomal regions, through HUMARA, ZDHHC15 gene assay and the novel 5-ethynyl-2 0 -deoxyuridine (EdU) incorporation assay, and identified an extremely skewed XCI pattern toward the derivative chromosomes for all the patients, and a variable pattern of late-replication on the autosomal regions of the derivative chromosomes. All patients showed phenotypical overlap with patients presenting deletions of the autosomal late-replicating regions, suggesting that the inactivation of autosomal segments may be responsible for their phenotype. Our data highlight the importance of the XCI spread into autosomal regions for establishing the clinical picture in patients carrying unbalanced X-autosome translocations, and the incorporation of EdU as a novel and precise tool to evaluate the inactivation status in such patients.

Prenatal diagnosis of dicentric chromosome X mosaicism: a case report and review

“…The pseudo dicentric chromosome 45, X, psu dic (X; 18) (p11.2; p11.2) indicated by the C-band karyotype is an unbalanced X-autosome translocation. Some unbalanced X-autosome translocations have been reported to be preferentially inactivated, which could spread X chromosome inactivation (XCI) into the autosomal chromosome regions and inactivate autosomal genes ( Favilla et al, 2021 ). We could not measure the extent of the spreading into the translocated 18.…”

Real-Time Observation of “Soft” Magic-Size Clusters during Hydrolysis of the Model Metallodrug Bismuth Disalicylate

“…[2021] [13], revealed inactivation of the maternal and paternal alleles in the ratio of 71% and 29%, respectively, with the normal allele being preferentially inactive. Her mother presented a skewed XCI towards a different allele (78%:22%) (Fig.…”