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

ABSTRACT:

Background

Structural variants (SVs) that disrupt topologically associating domains (TADs) can cause disease by rewiring enhancer-promoter interactions. Duplications involving GPR101 are known to cause X-linked acrogigantism (X-LAG) by enabling aberrant expression of GPR101 through hijacking of enhancers at VGLL1. However, not all GPR101-containing duplications are pathogenic, presenting a diagnostic challenge, especially in the prenatal setting.

Methods

We evaluated POSTRE, a tool designed to predict the regulatory impact of SVs, to distinguish pathogenic from benign GPR101 duplications. We analyzed six non-pathogenic duplications, and 27 known X-LAG associated pathogenic duplications. Tissue-specific enhancer maps built using H3K27ac ChIP

SUBMITTER: Trivellin G 

PROVIDER: S-EPMC12236931 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature