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

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.