Next generation sequencing identifies mutations in Atonal homolog 7 (ATOH7) in families with global eye developmental defects
| Autor: | Eamonn Sheridan, Graham R. Taylor, Joanne E. Morgan, Narcis Fernandez-Fuentes, Hussain Jafri, Ahmed Al-Maskari, Özlem Yenice, Colin A. Johnson, Clare V. Logan, Carmel Toomes, Nursel Elcioglu, Manir Ali, Yasmin Raashid, David A. Parry, Martin McKibbin, Chris F. Inglehearn, Kamron N. Khan, Moin Mohamed, Zakia Abdelhamed, James A. Poulter, Ian M. Carr |
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| Přispěvatelé: | Khan, Kamron, Logan, Clare V., McKibbin, Martin, Sheridan, Eamonn, Elcioglu, Nursel H., Yenice, Ozlem, Parry, David A., Fernandez-Fuentes, Narcis, Abdelhamed, Zakia I. A., Al-Maskari, Ahmed, Poulter, James A., Mohamed, Moin D., Carr, Ian M., Morgan, Joanne E., Jafri, Hussain, Raashid, Yasmin, Taylor, Graham R., Johnson, Colin A., Inglehearn, Chris F., Toomes, Carmel, Ali, Manir |
| Rok vydání: | 2011 |
| Předmět: |
Male
Eye Diseases genetic structures DNA Mutational Analysis Nerve Tissue Proteins Biology Eye Microphthalmia Retina Consanguinity 03 medical and health sciences 0302 clinical medicine NORRIE-DISEASE VASCULATURE Basic Helix-Loop-Helix Transcription Factors Genetics medicine Humans Eye Abnormalities GENOME-WIDE ASSOCIATION Eye Proteins FZD4 MUTATIONS Persistent fetal vasculature Molecular Biology beta Catenin Genetics (clinical) 030304 developmental biology 0303 health sciences Optic nerve hypoplasia Articles General Medicine EXUDATIVE VITREORETINOPATHY medicine.disease eye diseases ATONAL HOMOLOG Microcornea medicine.anatomical_structure Persistent hyperplastic primary vitreous Mutation 030221 ophthalmology & optometry Congenital cataracts Optic nerve RETINAL GANGLION-CELL FATE DETERMINATION sense organs OPEN-ANGLE GLAUCOMA OPTIC-NERVE |
| Zdroj: | Human Molecular Genetics |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | The atonal homolog 7 (ATOH7) gene encodes a transcription factor involved in determining the fate of retinal progenitor cells and is particularly required for optic nerve and ganglion cell development. Using a combination of autozygosity mapping and next generation sequencing, we have identified homozygous mutations in this gene, p.E49V and p.P18RfsX69, in two consanguineous families diagnosed with multiple ocular developmental defects, including severe vitreoretinal dysplasia, optic nerve hypoplasia, persistent fetal vasculature, microphthalmia, congenital cataracts, microcornea, corneal opacity and nystagmus. Most of these clinical features overlap with defects in the Norrin/beta-catenin signalling pathway that is characterized by dysgenesis of the retinal and hyaloid vasculature. Our findings document Mendelian mutations within ATOH7 and imply a role for this molecule in the development of structures at the front as well as the back of the eye. This work also provides further insights into the function of ATOH7, especially its importance in retinal vascular development and hyaloid regression. |
| Databáze: | OpenAIRE |
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