Comprehensive multigene testing needed in diagnosing cholestasis

A testing program created to discover the genetic causes of cholestasis highlighted the benefit of using comprehensive rapid multigene testing when diagnosing cholestasis, according to newly published data.

In this study, a total of 2433 samples from patients with a history of cholestasis without a known cause or unexplained chronic liver disease, were submitted for a neonatal/adult sequencing panel containing 66 genes relevant to cholestasis. Overall, 2171 results were reported within a median time of 21 days.

There were 583 pathogenic variants, 79 likely pathogenic variants, and 3117 variants of unknown significance. A total of 166 pathogenic/likely pathogenic variants and 515 variants of unknown significance were novel.

JAG1 + NOTCH2 (Alagille syndrome), ABCB11, SERPINA1, ABCB4, and POLG were the most common genetic diagnoses. The panel’s overall diagnostic yield was 12%.

Reference
Karpen SJ, Kamath BM, Alexander JJ, et al. Use of a comprehensive 66-gene cholestasis sequencing panel in 2171 cholestatic infants, children, and young adults. J Pediatr Gastroenterol Nutr. 2021;72(5):654-660. doi: 10.1097/MPG.0000000000003094. PMID: 33720099.