Functional Characteristics of Diverse PAX6 Mutations Associated With Isolated Foveal Hypoplasia

• DOI: 10.20944/preprints202306.1772.v1
• Publication Date: 2023-06-27T00:52:11Z
• Authors: Itsuka Matsushita; Hiroto Izumi; Shinji Ueno; Takaaki Hayashi; Kaoru Fujinami; Kazushige Tsunoda; Takeshi Iwata; Yoshiaki Kiuchi; Hiroyuki Kondo
• Keywords: PAX6; Aniridia

Autosomal dominant isolated foveal hypoplasia (FVH1) is a rare condition of (FH) that lacks any other ocular manifestations. FVH1 associated with hypomorphic mutations in the PAX6 gene. We report our findings 17 patients or FH aniridia and corneal opacities. Patients three mutations, p.V78E, p.V83F p.R128H, C-terminal subdomain paired domain (CTS) consistently had severe FH. Luciferase assays indicated transcriptional activities these were significantly reduced comparable to truncation mutation p.G65Rfs*5. p.P20S N-terminal domain, patient p.N365K proline-serine-threonine-rich (PSTD) mild A p.Q255L homeodomain The P20S Q255L mutants did not affect activity. Mutant N365K retained DNA binding activity but due low PSTD transactivation. These demonstrated underlie functional divergence between ability Broadly distributed gene, limited CST region, responsible for FVH1.