Genetic analysis of an asymptomatic female with a large Xp deletion revealed insights into the X chromosome inactivation pattern: a case report.

BACKGROUND

X-linked disorders caused by skewed X chromosome inactivation (XCI) result in phenotypic heterogeneity, which is rarely reported. XCI testing is not widely used in clinical cases, making risk assessment for carriers of X-linked unbalanced structural abnormalities challenging.

CASE PRESENTATION: We present genetic data from an asymptomatic female with a de novo 6.31 Mb deletion on Xp11.23-p11.22, identified through CMA-array analysis. The deletion includes 101 OMIM genes, 11 haplo-insufficient (HI) genes, and 4 escape genes. An androgen receptor (AR) methylation assay showed a 100% skewed XCI pattern silencing the abnormal X-chromosome. RNA-seq analysis revealed up-regulation of escape genes within the deletion at the transcriptional level. The absence of a severe clinical phenotype, aside from infertility, in this female was most likely attributed to the extremely skewed XCI and the compensatory up-regulation of XCI escape genes.

CONCLUSIONS

Our data indicate that XCI can modify the phenotype in female carriers of heterozygous X-linked deletion and provide valuable information about the analysis of XCI pattern in risk assessment of this kind cases, especially precious fetuses.