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 - © 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.
U2 - 10.1038/s41525-022-00334-9
DO - 10.1038/s41525-022-00334-9
M3 - Article
C2 - 36351915
SN - 2056-7944
VL - 7
SP - 65
JO - npj Genomic Medicine
JF - npj Genomic Medicine
IS - 1
ER -