13.06.2024Limited Added Diagnostic Value of Whole Genome Sequencing in Genetic Testing of Inherited Retinal Diseases in a Swiss Patient Cohort

WGS was performed for index patients in 66 families. The datasets were analyzed according to GATK's guidelines. Additionally, DeepVariant was complemented by GATK's workflow, and a novel structural variant pipeline was developed.

Overall, a molecular diagnosis was established in 19/66 (28.8%) index patients. Pathogenic deletions and one deep-intronic variant contributed to the diagnostic yield in 4/19 and 1/19 index patients, respectively. The remaining diagnoses (14/19) were attributed to exonic variants that were missed during WES analysis due to bioinformatic limitations, newly described loci, or unclear pathogenicity. The added diagnostic value of WGS equals 5/66 (9.6%) for our cohort, which is comparable to previous studies. This figure would decrease further to 1/66 (1.5%) with a standardized and reliable copy number variant workflow during WES analysis.

Given the higher costs and limited added value, the implementation of WGS as a first-tier assay for inherited eye disorders in a diagnostic laboratory remains untimely. Instead, progress in bioinformatic tools and communication between diagnostic and clinical teams have the potential to ameliorate diagnostic yields.

Keywords: 

added diagnostic value; copy number variants (CNVs); deep-intronic variants; diagnostic yield; genetic testing; inherited retinal dystrophy (IRD); molecular diagnostics; structural variants (SVs); whole exome sequencing (WES); whole genome sequencing (WGS).

Read the full publication here:

Limited Added Diagnostic Value of Whole Genome Sequencing in Genetic Testing of Inherited Retinal Diseases in a Swiss Patient Cohort
PMID: 38928247, S2CID: 270544549, DOI: 10.3390/ijms25126540, International Journal of Molecular Sciences, 25(6540):1-15. Jun 13 2024.

Authors:

Jordi Maggi, Samuel Koller, Silke Feil, Ruxandra Bachmann-Gagescu, Christina Gerth-Kahlert & Wolfgang Berger