TY - JOUR
T1 - Diagnostic analysis of the highly complex OPN1LW/OPN1MW gene cluster using long-read sequencing and MLPA
AU - Haer-Wigman, Lonneke
AU - den Ouden, Amber
AU - van Genderen, Maria M
AU - Kroes, Hester Y
AU - Verheij, Joke
AU - Smailhodzic, Dzenita
AU - Hoekstra, Attje S
AU - Vijzelaar, Raymon
AU - Blom, Jan
AU - Derks, Ronny
AU - Tjon-Pon-Fong, Menno
AU - Yntema, Helger G
AU - Nelen, Marcel R
AU - Vissers, Lisenka E L M
AU - Lugtenberg, Dorien
AU - Neveling, Kornelia
N1 - Funding Information:
We would like to thank Christian Gilissen for checking the figures for visibility for persons with color vision deficiencies. We would like to thank Ronald van Beek and Eveline Kamping for performing the OGM.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/11/9
Y1 - 2022/11/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85141626101&partnerID=8YFLogxK
U2 - 10.1038/s41525-022-00334-9
DO - 10.1038/s41525-022-00334-9
M3 - Article
C2 - 36351915
VL - 7
JO - npj Genomic Medicine
JF - npj Genomic Medicine
IS - 1
M1 - 65
ER -