Disruption of the topologically associated domain at Xp21.2 is related to 46,XY gonadal dysgenesis.

ABSTRACT:

Background

Duplications at the Xp21.2 locus have previously been linked to 46,XY gonadal dysgenesis (GD), which is thought to result from gene dosage effects of NR0B1 (DAX1), but the exact disease mechanism remains unknown.

Methods

Patients with 46,XY GD were analysed by whole genome sequencing. Identified structural variants were confirmed by array CGH and analysed by high-throughput chromosome conformation capture (Hi-C).

Results

We identified two unrelated patients: one showing a complex rearrangement upstream of NR0B1 and a second harbouring a 1.2 Mb triplication, including NR0B1. Whole genome sequencing and Hi-C analysis revealed the rewiring of a topological-associated domain (TAD) boundary close to NR0B1 associated with neo-TA

SUBMITTER: Meinel JA 

PROVIDER: S-EPMC10176412 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature