First submicroscopic inversion of the OPA1 gene identified in dominant optic atrophy – a case report
Abstract Background Dominant optic atrophy (DOA) is an inherited optic neuropathy that mainly affects visual acuity, central visual fields and color vision due to a progressive loss of retinal ganglion cells and their axons that form the optic nerve. Approximately 45–90% of affected individuals with...
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BMC
2020-11-01
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| Series: | BMC Medical Genetics |
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| Online Access: | http://link.springer.com/article/10.1186/s12881-020-01166-z |
| _version_ | 1818460520524546048 |
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| author | Nicole Weisschuh Pascale Mazzola Tilman Heinrich Tobias Haack Bernd Wissinger Felix Tonagel Carina Kelbsch |
| author_facet | Nicole Weisschuh Pascale Mazzola Tilman Heinrich Tobias Haack Bernd Wissinger Felix Tonagel Carina Kelbsch |
| author_sort | Nicole Weisschuh |
| collection | DOAJ |
| description | Abstract Background Dominant optic atrophy (DOA) is an inherited optic neuropathy that mainly affects visual acuity, central visual fields and color vision due to a progressive loss of retinal ganglion cells and their axons that form the optic nerve. Approximately 45–90% of affected individuals with DOA harbor pathogenic variants in the OPA1 gene. The mutation spectrum of OPA1 comprises nonsense, canonical and non-canonical splice site, frameshift and missense as well as copy number variants, but intragenic inversions have not been reported so far. Case presentation We report a 33-year-old male with characteristic clinical features of DOA. Whole-genome sequencing identified a structural variant of 2.4 kb comprising an inversion of 937 bp at the OPA1 locus. Fine mapping of the breakpoints to single nucleotide level revealed that the structural variation was an inversion flanked by two deletions. As this rearrangement inverts the entire first exon of OPA1, it was classified as likely pathogenic. Conclusions We report the first DOA case harboring an inversion in the OPA1 gene. Our study demonstrates that copy-neutral genomic rearrangements have to be considered as a possible cause of disease in DOA cases. |
| first_indexed | 2024-12-14T23:31:33Z |
| format | Article |
| id | doaj.art-6a1a22669217408c975b8ab2ef492b6c |
| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-14T23:31:33Z |
| publishDate | 2020-11-01 |
| publisher | BMC |
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| spelling | doaj.art-6a1a22669217408c975b8ab2ef492b6c2022-12-21T22:43:41ZengBMCBMC Medical Genetics1471-23502020-11-012111610.1186/s12881-020-01166-zFirst submicroscopic inversion of the OPA1 gene identified in dominant optic atrophy – a case reportNicole Weisschuh0Pascale Mazzola1Tilman Heinrich2Tobias Haack3Bernd Wissinger4Felix Tonagel5Carina Kelbsch6Institute for Ophthalmic Research, Centre for Ophthalmology, University of TübingenInstitute of Medical Genetics and Applied Genomics, University of TübingenInstitute of Medical Genetics and Applied Genomics, University of TübingenInstitute of Medical Genetics and Applied Genomics, University of TübingenInstitute for Ophthalmic Research, Centre for Ophthalmology, University of TübingenUniversity Eye Hospital, Centre for Ophthalmology, University of TübingenUniversity Eye Hospital, Centre for Ophthalmology, University of TübingenAbstract Background Dominant optic atrophy (DOA) is an inherited optic neuropathy that mainly affects visual acuity, central visual fields and color vision due to a progressive loss of retinal ganglion cells and their axons that form the optic nerve. Approximately 45–90% of affected individuals with DOA harbor pathogenic variants in the OPA1 gene. The mutation spectrum of OPA1 comprises nonsense, canonical and non-canonical splice site, frameshift and missense as well as copy number variants, but intragenic inversions have not been reported so far. Case presentation We report a 33-year-old male with characteristic clinical features of DOA. Whole-genome sequencing identified a structural variant of 2.4 kb comprising an inversion of 937 bp at the OPA1 locus. Fine mapping of the breakpoints to single nucleotide level revealed that the structural variation was an inversion flanked by two deletions. As this rearrangement inverts the entire first exon of OPA1, it was classified as likely pathogenic. Conclusions We report the first DOA case harboring an inversion in the OPA1 gene. Our study demonstrates that copy-neutral genomic rearrangements have to be considered as a possible cause of disease in DOA cases.http://link.springer.com/article/10.1186/s12881-020-01166-zCase reportInversionComplex rearrangementDominant optic atrophyOPA1Non-homologous end joining (NHEJ) |
| spellingShingle | Nicole Weisschuh Pascale Mazzola Tilman Heinrich Tobias Haack Bernd Wissinger Felix Tonagel Carina Kelbsch First submicroscopic inversion of the OPA1 gene identified in dominant optic atrophy – a case report BMC Medical Genetics Case report Inversion Complex rearrangement Dominant optic atrophy OPA1 Non-homologous end joining (NHEJ) |
| title | First submicroscopic inversion of the OPA1 gene identified in dominant optic atrophy – a case report |
| title_full | First submicroscopic inversion of the OPA1 gene identified in dominant optic atrophy – a case report |
| title_fullStr | First submicroscopic inversion of the OPA1 gene identified in dominant optic atrophy – a case report |
| title_full_unstemmed | First submicroscopic inversion of the OPA1 gene identified in dominant optic atrophy – a case report |
| title_short | First submicroscopic inversion of the OPA1 gene identified in dominant optic atrophy – a case report |
| title_sort | first submicroscopic inversion of the opa1 gene identified in dominant optic atrophy a case report |
| topic | Case report Inversion Complex rearrangement Dominant optic atrophy OPA1 Non-homologous end joining (NHEJ) |
| url | http://link.springer.com/article/10.1186/s12881-020-01166-z |
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