DNA methylation analysis of ade novo balanced X;13 translocation in a girl with abnormal phenotype: evidence for functional duplication of the whole short arm of the X chromosome

Abstract

We report on a 13-month-old girl showing dysmorphic features and a delay in psychomotor development. She was diagnosed with a balanced de novo translocation 46,X,t(X;13)(p11.2;p13) and non-random inactivation of the X chromosome. FISH analysis, employing the X chromosome centromere and XIST-region-specific probes, showed that the XIST locus was not involved in the translocation. Selective inactivation of paternal X, which was involved in translocation, was revealed by the HUMARA assay. The pattern of methylation of 5 genes located within Xp, which are normally silenced on an inactive X chromosome, corresponded to an active (unmethylated) X chromosome. These results revealed that in our proband the X chromosome involved in translocation (Xt) was preferentially inactivated. However, genes located on the translocated Xp did not include XIST. This resulted in functional Xp disomy, which most probably accounts for the abnormal phenotype in our patient.

Functional monosomy of 6q27‐qter and functional disomy of Xpter‐p22.11 due to X;6 translocation with an atypical X‐inactivation pattern

“…Similarly, functional Xp disomy has also been described in a girl with developmental delay and the karyotype 46,X, t(X;13)(p11.2;p13). She also had skewed XCI with a preferentially inactivated derivative X chromosome, however, the breakpoint at Xp11.2 has not been fine-mapped in this case (Myszka et al, 2010). In our case, RBA banding did not show any observable bright region at the tip of the p arm of the rearranged X suggesting that the translocated terminal part of 6q was inactivated (Figure 4A).…”