Mutations in SAMD7 cause autosomal-recessive macular dystrophy with or without cone dysfunction

Miriam Bauwens, Elifnaz Celik, Dinah Zur, Siying Lin, Mathieu Quinodoz, Michel Michaelides, Andrew R. Webster, Filip Van Den Broeck, Bart P. Leroy, Leah Rizel, Abigail R. Moye, Audrey Meunier, Hoai Viet Tran, Alexandre P. Moulin, Quinten Mahieu, Mattias Van Heetvelde, Gavin Arno, Carlo Rivolta, Elfride De Baere, Tamar Ben-Yosef

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)393-402
Number of pages10
JournalAmerican Journal of Human Genetics
Issue number2
StatePublished - 1 Feb 2024


  • Animals
  • Eye Abnormalities
  • Homeodomain Proteins/genetics
  • Humans
  • Macular Degeneration/genetics
  • Mice
  • Mutation/genetics
  • Retina
  • SAMD7
  • Trans-Activators/genetics
  • inherited retinal diseases
  • macular dystrophy
  • mutation
  • retina

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Genetics


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