Diagnostic analysis of the highly complex OPN1LW/OPN1MW gene cluster using long-read sequencing and MLPA

Lonneke Haer-Wigman, Amber den Ouden, Maria M van Genderen, Hester Y Kroes, Joke Verheij, Dzenita Smailhodzic, Attje S Hoekstra, Raymon Vijzelaar, Jan Blom, Ronny Derks, Menno Tjon-Pon-Fong, Helger G Yntema, Marcel R Nelen, Lisenka E L M Vissers, Dorien Lugtenberg, Kornelia Neveling

Research output: Contribution to journalArticleResearchpeer-review


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.

Original languageEnglish
Pages (from-to)65
Journalnpj Genomic Medicine
Issue number1
Publication statusPublished - 9 Nov 2022


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