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

Area of Science:

• Genetics
• Ophthalmology
• Molecular Biology

Background:

• Sterile alpha motif domain containing 7 (SAMD7) is part of Polycomb repressive complex 1.
• This complex inhibits gene transcription, including genes regulated by Cone-Rod Homeobox (CRX).

Purpose of the Study:

• To investigate the role of SAMD7 in human retinal function.
• To identify genetic mutations in SAMD7 causing retinal diseases.

Main Methods:

• Identification of bi-allelic mutations in SAMD7.
• In vitro assays to assess the impact of mutations on CRX-dependent promoter activity.
• Immunostaining of human retinal sections to determine SAMD7 localization.

Main Results:

• Bi-allelic mutations in SAMD7 cause autosomal-recessive macular dystrophy, potentially with cone dysfunction.
• Four mutations identified affect SAMD7 splicing.
• A missense mutation alters SAMD7's repressive effect on CRX activity.
• SAMD7 is localized in the nuclei of human retinal cells, including rods, cones, and inner nuclear layer cells.

Conclusions:

• SAMD7 is essential for human retinal function.
• The identified SAMD7 mutations are a novel cause of inherited macular dystrophy.
• SAMD7 plays a different role in the human retina compared to the mouse retina.