Whole-genome sequencing reveals large ATP8B1 deletion / duplications as “second mutations” missed by exome-based sequencing

This study sought second pathogenic variants in ATP8B1 by whole-genome sequencing (WGS) in 4 unrelated low-GGT cholestasis patients in whom clinical suspicion of PFIC1 was high and gene-panel or Sanger sequencing had identified only one pathogenic variant in ATP8B1. Sanger sequencing confirmed WGS findings and determined the origin of each variant. Novel non-recurrent structural variants in 3 patients (P1 – P3) were identified in trans: g.55396652_55403080del (6427bp deletion), g.55335906_55346620dup (10,715bp duplication), and g.55362063_55364293dup (2231bp duplication).
Source: Journal of Molecular Diagnostics - Category: Pathology Authors: Source Type: research