Phenotypic Variation in a Four-Generation Family with Aniridia Carrying a Novel PAX6 Mutation
Aniridia is a congenital disease that affects almost all eye structures and is primarily caused by loss-of-function mutations in the PAX6 gene. The degree of vision loss in aniridia varies and is dependent on the extent of foveal, iris, and optic nerve hypoplasia and the presence of glaucoma, catara...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Journal of Ophthalmology |
| Online Access: | http://dx.doi.org/10.1155/2018/5978293 |
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| author | Grace M. Wang Lev Prasov Hayder Al-Hasani Colin E. R. Marrs Sahil Tolia Laurel Wiinikka-Buesser Julia E. Richards Brenda L. Bohnsack |
| author_facet | Grace M. Wang Lev Prasov Hayder Al-Hasani Colin E. R. Marrs Sahil Tolia Laurel Wiinikka-Buesser Julia E. Richards Brenda L. Bohnsack |
| author_sort | Grace M. Wang |
| collection | DOAJ |
| description | Aniridia is a congenital disease that affects almost all eye structures and is primarily caused by loss-of-function mutations in the PAX6 gene. The degree of vision loss in aniridia varies and is dependent on the extent of foveal, iris, and optic nerve hypoplasia and the presence of glaucoma, cataracts, and corneal opacification. Here, we describe a 4-generation family in which 7 individuals across 2 generations carry a novel disease-causing frameshift mutation (NM_000280.4(PAX6):c.565TC>T) in PAX6. This mutation results in an early stop codon in exon 8, which is predicted to cause nonsense-mediated decay of the truncated mRNA and a functionally null PAX6 allele. Family members with aniridia showed differences in multiple eye phenotypes including iris and optic nerve hypoplasia, congenital and acquired corneal opacification, glaucoma, and strabismus. Visual acuity ranged from 20/100 to less than 20/800. Patients who required surgical intervention for glaucoma or corneal opacification had worse visual outcomes. Our results show that family members carrying a novel PAX6 frameshift mutation have variable expressivity, leading to different ocular comorbidities and visual outcomes. |
| format | Article |
| id | doaj-art-cc4155e57d2d4017bc5ca6e6f5f53c88 |
| institution | OA Journals |
| issn | 2090-004X 2090-0058 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Ophthalmology |
| spelling | doaj-art-cc4155e57d2d4017bc5ca6e6f5f53c882025-08-20T02:19:57ZengWileyJournal of Ophthalmology2090-004X2090-00582018-01-01201810.1155/2018/59782935978293Phenotypic Variation in a Four-Generation Family with Aniridia Carrying a Novel PAX6 MutationGrace M. Wang0Lev Prasov1Hayder Al-Hasani2Colin E. R. Marrs3Sahil Tolia4Laurel Wiinikka-Buesser5Julia E. Richards6Brenda L. Bohnsack7Department of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, The University of Michigan, Ann Arbor, MI 48105, USADepartment of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, The University of Michigan, Ann Arbor, MI 48105, USADepartment of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, The University of Michigan, Ann Arbor, MI 48105, USADepartment of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, The University of Michigan, Ann Arbor, MI 48105, USADepartment of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, The University of Michigan, Ann Arbor, MI 48105, USADepartment of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, The University of Michigan, Ann Arbor, MI 48105, USADepartment of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, The University of Michigan, Ann Arbor, MI 48105, USADepartment of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, The University of Michigan, Ann Arbor, MI 48105, USAAniridia is a congenital disease that affects almost all eye structures and is primarily caused by loss-of-function mutations in the PAX6 gene. The degree of vision loss in aniridia varies and is dependent on the extent of foveal, iris, and optic nerve hypoplasia and the presence of glaucoma, cataracts, and corneal opacification. Here, we describe a 4-generation family in which 7 individuals across 2 generations carry a novel disease-causing frameshift mutation (NM_000280.4(PAX6):c.565TC>T) in PAX6. This mutation results in an early stop codon in exon 8, which is predicted to cause nonsense-mediated decay of the truncated mRNA and a functionally null PAX6 allele. Family members with aniridia showed differences in multiple eye phenotypes including iris and optic nerve hypoplasia, congenital and acquired corneal opacification, glaucoma, and strabismus. Visual acuity ranged from 20/100 to less than 20/800. Patients who required surgical intervention for glaucoma or corneal opacification had worse visual outcomes. Our results show that family members carrying a novel PAX6 frameshift mutation have variable expressivity, leading to different ocular comorbidities and visual outcomes.http://dx.doi.org/10.1155/2018/5978293 |
| spellingShingle | Grace M. Wang Lev Prasov Hayder Al-Hasani Colin E. R. Marrs Sahil Tolia Laurel Wiinikka-Buesser Julia E. Richards Brenda L. Bohnsack Phenotypic Variation in a Four-Generation Family with Aniridia Carrying a Novel PAX6 Mutation Journal of Ophthalmology |
| title | Phenotypic Variation in a Four-Generation Family with Aniridia Carrying a Novel PAX6 Mutation |
| title_full | Phenotypic Variation in a Four-Generation Family with Aniridia Carrying a Novel PAX6 Mutation |
| title_fullStr | Phenotypic Variation in a Four-Generation Family with Aniridia Carrying a Novel PAX6 Mutation |
| title_full_unstemmed | Phenotypic Variation in a Four-Generation Family with Aniridia Carrying a Novel PAX6 Mutation |
| title_short | Phenotypic Variation in a Four-Generation Family with Aniridia Carrying a Novel PAX6 Mutation |
| title_sort | phenotypic variation in a four generation family with aniridia carrying a novel pax6 mutation |
| url | http://dx.doi.org/10.1155/2018/5978293 |
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