articlenpj Genomic MedicineJan 15, 2026GOLD OA

Distinguishing benign from pathogenic duplications involving GPR101 and VGLL1-adjacent enhancers in the clinical setting with the bioinformatic tool POSTRE

GTGiampaolo TrivellinVSVíctor Sánchez-GayaAGAlexia GrassoMPMagdalena PasińskaCAConstantine A. Stratakis

Humanitas University · IRCCS Humanitas Research Hospital · +13 more institutions

PubMed
Indexed incrossrefdoajpubmed

Abstract

Structural variants (SVs) that disrupt topologically associating domains can cause disease by rewiring enhancer-promoter interactions. Duplications involving GPR101 are known to cause X-linked acrogigantism (X-LAG) through ectopic GPR101 expression, but not all of these duplications are pathogenic. This presents a diagnostic challenge, especially in the prenatal setting. We evaluated POSTRE, a tool that predicts the regulatory impact of SVs, to distinguish pathogenic from benign GPR101 duplications. We analyzed seven non-pathogenic duplications and 27 known X-LAG-associated duplications. To enable predictions in an X-LAG-relevant tissue, enhancer maps built using H3K27ac ChIP-seq, ATAC-seq, and RNA-seq data…

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13

Topics & keywords

Topics
Keywords
  • Enhancer
  • Chromatin
  • Genome
  • Gene duplication
  • Segmental duplication
  • Disease
  • Clinical diagnosis
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