Skewed X-Chromosome Inactivation and Compensatory Upregulation of Escape Genes Precludes Major Clinical Symptoms in a Female With a Large Xq Deletion.

ABSTRACT: In mammalian females, X-chromosome inactivation (XCI) acts as a dosage compensation mechanism that equalizes X-linked genes expression between homo- and heterogametic sexes. However, approximately 12-23% of X-linked genes escape from XCI, being bi-allelic expressed. Herein, we report on genetic and functional data from an asymptomatic female of a Fragile X syndrome family, who harbors a large deletion on the X-chromosome. Array-CGH uncovered that the de novo, terminal, paternally originated 32 Mb deletion on Xq25-q28 spans 598 RefSeq genes, including escape and variable escape genes. Androgen receptor (AR) and retinitis pigmentosa 2 (RP2) methylation assays showed extreme skewed XCI ratios from both peripheral blood and buccal mucosa, silencing the abnormal X-chromosom

SUBMITTER: Santos-Reboucas CB 

PROVIDER: S-EPMC7064548 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature