We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Diagnostic analysis of the highly complex OPN1LW/OPN1MW gene cluster using long-read sequencing and MLPA.
- 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; Tjon-Pon-Fong, Menno; Yntema, Helger G.; Nelen, Marcel R.; Vissers, Lisenka E.L.M.; Lugtenberg, Dorien; Neveling, Kornelia
- 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.
- Subjects
GENE clusters; DNA copy number variations; NUCLEOTIDE sequencing; VISION disorders; GENETIC variation; SEQUENCE analysis
- Publication
NPJ Genomic Medicine, 2022, Vol 7, Issue 1, p1
- ISSN
2056-7944
- Publication type
Article
- DOI
10.1038/s41525-022-00334-9