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| Item Type: | Article |
|---|---|
| Title: | Homozygous frameshift mutations in FAT1 cause a syndrome characterized by colobomatous-microphthalmia, ptosis, nephropathy and syndactyly |
| Creators Name: | Lahrouchi, N. and George, A. and Ratbi, I. and Schneider, R. and Elalaoui, S.C. and Moosa, S. and Bharti, S. and Sharma, R. and Abu-Asab, M. and Onojafe, F. and Adadi, N. and Lodder, E.M. and Laarabi, F.Z. and Lamsyah, Y. and Elorch, H. and Chebbar, I. and Postma, A.V. and Lougaris, V. and Plebani, A. and Altmueller, J. and Kyrieleis, H. and Meiner, V. and McNeill, H. and Bharti, K. and Lyonnet, S. and Wollnik, B. and Henrion-Caude, A. and Berraho, A. and Hildebrandt, F. and Bezzina, C.R. and Brooks, B.P. and Sefiani, A. |
| Abstract: | A failure in optic fissure fusion during development can lead to blinding malformations of the eye. Here, we report a syndrome characterized by facial dysmorphism, colobomatous microphthalmia, ptosis and syndactyly with or without nephropathy, associated with homozygous frameshift mutations in FAT1. We show that Fat1 knockout mice and zebrafish embryos homozygous for truncating fat1a mutations exhibit completely penetrant coloboma, recapitulating the most consistent developmental defect observed in affected individuals. In human retinal pigment epithelium (RPE) cells, the primary site for the fusion of optic fissure margins, FAT1 is localized at earliest cell-cell junctions, consistent with a role in facilitating optic fissure fusion during vertebrate eye development. Our findings establish FAT1 as a gene with pleiotropic effects in human, in that frameshift mutations cause a severe multi-system disorder whereas recessive missense mutations had been previously associated with isolated glomerulotubular nephropathy. |
| Keywords: | Disease Genetics, Eye Diseases, Genetics of the Nervous System, Medical Genetics |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 10 |
| Number: | 1 |
| Page Range: | 1180 |
| Date: | 12 March 2019 |
| Official Publication: | https://doi.org/10.1038/s41467-019-08547-w |
| PubMed: | View item in PubMed |
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