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

doi:10.1038/s41525-022-00334-9

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

Medical retina and Uveitis

Research output: Contribution to journal › Article › Research › peer-review

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.

Original language	English
Pages (from-to)	65
Journal	npj Genomic Medicine
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41525-022-00334-9
Publication status	Published - 9 Nov 2022

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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, 7(1), 65. https://doi.org/10.1038/s41525-022-00334-9

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

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.",

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

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Haer-Wigman, L, den Ouden, A, van Genderen, MM, Kroes, HY, Verheij, J, Smailhodzic, D, Hoekstra, AS, Vijzelaar, R, Blom, J, Derks, R, Tjon-Pon-Fong, M, Yntema, HG, Nelen, MR, Vissers, LELM, 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, pp. 65. https://doi.org/10.1038/s41525-022-00334-9

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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

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.

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DO - 10.1038/s41525-022-00334-9

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SN - 2056-7944

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SP - 65

JO - npj Genomic Medicine

JF - npj Genomic Medicine

IS - 1

ER -

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

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