Diagnostic analysis of the highly complex OPN1LW/OPN1MW gene cluster using long-read sequencing and MLPA
Publication date
2022-11-09
Authors
Haer-Wigman, Lonneke
den Ouden, Amber
van Genderen, Maria M.
Kroes, Hester Y
Verheij, Joke
Smailhodzic, Dzenita
Hoekstra, Attje S
Vijzelaar, Raymon
Blom, Jan
Derks, Ronny
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Abstract
Pathogenic variants in the OPN1LW/OPN1MW gene cluster are causal for a range of mild to severe visual impairments with color deficiencies. The widely utilized short-read next-generation sequencing (NGS) is inappropriate for the analysis of the OPN1LW/OPN1MW gene cluster and many patients with pathogenic variants stay underdiagnosed. A diagnostic genetic assay was developed for the OPN1LW/OPN1MW gene cluster, consisting of copy number analysis via multiplex ligation-dependent probe amplification and sequence analysis via long-read circular consensus sequencing. Performance was determined on 50 clinical samples referred for genetic confirmation of the clinical diagnosis (n = 43) or carrier status analysis (n = 7). A broad range of pathogenic haplotypes were detected, including deletions, hybrid genes, single variants and combinations of variants. The developed genetic assay for the OPN1LW/OPN1MW gene cluster is a diagnostic test that can detect both structural and nucleotide variants with a straightforward analysis, improving diagnostic care of patients with visual impairment.
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Journal Article
Citation
Haer-Wigman, L, den Ouden, A, van Genderen, M M, Kroes, H Y, Verheij, J, Smailhodzic, D, Hoekstra, A S, Vijzelaar, R, Blom, J, Derks, R, Tjon-Pon-Fong, M, Yntema, H G, Nelen, M R, Vissers, L E L M, Lugtenberg, D & Neveling, K 2022, 'Diagnostic analysis of the highly complex OPN1LW/OPN1MW gene cluster using long-read sequencing and MLPA', npj Genomic Medicine, vol. 7, no. 1, 65. https://doi.org/10.1038/s41525-022-00334-9