Work

Escape From X‐Chromosome Inactivation Enables Survival in a Male With an Unbalanced X;19 Translocation

Year: 2026

Type: article

Abstract: X;autosome translocations allow us to study how X-chromosome inactivation (XCI) spreads into autosomal DNA in vivo. We re-evaluated a male patient with an inherited unbalanced X;19 translocation to assess XCI-associated silencing of the translocated chromosome 19 segment. High-resolution SNP array analysis refined the rearrangement to a terminal 19p13.3 deletion of <0.21 Mb and a ∼95.4 Mb duplication spanning Xq11.1-Xqter. XCI testing showed opposite patterns in mother and son: the balanced carrier mother preferentially inactivated the normal X chromosome, whereas the proband preferentially inactivated der(19), which carries the duplicated Xq containing the X-inactivation center. To determine whether autosomal genes on der(19) were silenced, we performed allele-specific expression assays across chromosome 19 loci. Several informative loci showed biallelic expression in the proband, suggesting incomplete silencing of the translocated autosomal segment. Informative and less clearly interpretable loci were interspersed without an obvious positional gradient, favoring gene-specific variation in silencing susceptibility over a simple distance-dependent model. These findings are consistent with incomplete and heterogeneous silencing across the autosomal segment and provide a plausible molecular explanation for survival with this otherwise severe unbalanced rearrangement.

Source: Annals of the New York Academy of Sciences

DOI: 10.1111/nyas.70340

Authors: Onur Emre Onat, Tayfun Ozcelik

Institutions: Bezmiâlem Vakıf Üniversitesi, Bilkent University, National Nanotechnology Research Center

Language: English

Topic: Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $5,080