Bauwens, Miriam;
Celik, Elifnaz;
Zur, Dinah;
Lin, Siying;
Quinodoz, Mathieu;
Michaelides, Michel;
Webster, Andrew R;
... Ben-Yosef, Tamar; + view all
(2024)
Mutations in SAMD7 cause autosomal-recessive macular dystrophy with or without cone dysfunction.
The American Journal of Human Genetics
, 111
(2)
pp. 393-402.
10.1016/j.ajhg.2024.01.001.
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Abstract
Sterile alpha motif domain containing 7 (SAMD7) is a component of the Polycomb repressive complex 1, which inhibits transcription of many genes, including those activated by the transcription factor Cone-Rod Homeobox (CRX). Here we report bi-allelic mutations in SAMD7 as a cause of autosomal-recessive macular dystrophy with or without cone dysfunction. Four of these mutations affect splicing, while another mutation is a missense variant that alters the repressive effect of SAMD7 on CRX-dependent promoter activity, as shown by in vitro assays. Immunostaining of human retinal sections revealed that SAMD7 is localized in the nuclei of both rods and cones, as well as in those of cells belonging to the inner nuclear layer. These results place SAMD7 as a gene crucial for human retinal function and demonstrate a significant difference in the role of SAMD7 between the human and the mouse retina.
Type: | Article |
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Title: | Mutations in SAMD7 cause autosomal-recessive macular dystrophy with or without cone dysfunction |
Location: | United States |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1016/j.ajhg.2024.01.001 |
Publisher version: | http://dx.doi.org/10.1016/j.ajhg.2024.01.001 |
Language: | English |
Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
Keywords: | inherited retinal diseases, macular dystrophy, mutation, retina, SAMD7 |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
URI: | https://discovery.ucl.ac.uk/id/eprint/10188996 |
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