Article open access publication

De novo intrachromosomal gene conversion from OPN1MW to OPN1LW in the male germline results in Blue Cone Monochromacy

Scientific Reports, Springer Nature, ISSN 2045-2322

Volume 6, 1, 2016

DOI:10.1038/srep28253, Dimensions: pub.1046323914, PMC: PMC4919619, PMID: 27339364,



  1. (1) Institute for Ophthalmic Research, Centre for Ophthalmology, Tuebingen, Germany
  2. (2) Sankt Gertrauden Krankenhaus, grid.492055.f
  3. (3) Charité, grid.6363.0
  4. (4) Retina Foundation of the Southwest, grid.419187.2
  5. (5) Ghent University Hospital, grid.410566.0
  6. (6) Hôpitaux Universitaires de Strasbourg, grid.412220.7
  7. (7) Our Lady's Children's Hospital, grid.417322.1
  8. (8) Karolinska Institute, grid.4714.6
  9. (9) University Hospital of Montpellier, grid.157868.5
  10. (10) University of Michigan, grid.214458.e
  11. (11) Academic Medical Center, grid.5650.6
  12. (12) Department of Ophthalmology, University Medical Centre Groningen, University of Groningen, The Netherlands
  13. (13) Monash Medical Centre, grid.416060.5
  14. (14) Kennedy Center, grid.419352.8, Capital Region
  15. (15) Murdoch Children's Research Institute, grid.1058.c
  16. (16) Department of Medical Genetics, University Medical Centre Groningen, University of Groningen, The Netherlands
  17. (17) Oregon Health & Science University, grid.5288.7


X-linked cone dysfunction disorders such as Blue Cone Monochromacy and X-linked Cone Dystrophy are characterized by complete loss (of) or reduced L- and M- cone function due to defects in the OPN1LW/OPN1MW gene cluster. Here we investigated 24 affected males from 16 families with either a structurally intact gene cluster or at least one intact single (hybrid) gene but harbouring rare combinations of common SNPs in exon 3 in single or multiple OPN1LW and OPN1MW gene copies. We assessed twelve different OPN1LW/MW exon 3 haplotypes by semi-quantitative minigene splicing assay. Nine haplotypes resulted in aberrant splicing of ≥20% of transcripts including the known pathogenic haplotypes (i.e. 'LIAVA', 'LVAVA') with absent or minute amounts of correctly spliced transcripts, respectively. De novo formation of the 'LIAVA' haplotype derived from an ancestral less deleterious 'LIAVS' haplotype was observed in one family with strikingly different phenotypes among affected family members. We could establish intrachromosomal gene conversion in the male germline as underlying mechanism. Gene conversion in the OPN1LW/OPN1MW genes has been postulated, however, we are first to demonstrate a de novo gene conversion within the lineage of a pedigree.


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