Genome sequencing increases diagnostic yield in clinically diagnosed Alagille syndrome patients with previously negative test results.

ABSTRACT:

Purpose

Detection of all major classes of genomic variants in a single test would decrease cost and increase the efficiency of genomic diagnostics. Genome sequencing (GS) has the potential to provide this level of comprehensive detection. We sought to demonstrate the utility of GS in the molecular diagnosis of 18 patients with clinically defined Alagille syndrome (ALGS), who had a negative or inconclusive result by standard-of-care testing.

Methods

We performed GS on 16 pathogenic variant-negative probands and two probands with inconclusive results (of 406 ALGS probands) and analyzed the data for sequence, copy-number, and structural variants in JAG1 and NOTCH2.

Results

GS identified four novel pathogenic alterations including a copy-neutral inversion, a partial delet

SUBMITTER: Rajagopalan R 

PROVIDER: S-EPMC7862053 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature