Prevalence of IMPG1 and IMPG2 Mutations Leading to Retinitis Pigmentosa or Vitelliform Macular Dystrophy in a Cohort of Patients with Inherited Retinal Dystrophies.

Abstract

Background/objectives: The interphotoreceptor matrix proteoglycans 1 and 2 (IMPG1 and IMPG2) are two interdependent proteoglycans of the interphotoreceptor matrix (IPM). Mutations in IMPG1 or IMPG2 are linked to retinal diseases such as retinitis pigmentosa (RP) and vitelliform macular dystrophy (VMD), yet the specific mutations responsible for each condition remain undefined. This study identifies mutations in IMPG1 and IMPG2 linked to either RP or VMD. It also provides an in-depth in silico analysis of these mutations' structural and functional impact on protein domains, alongside a detailed examination of the corresponding disease phenotypes.

Methods: From a cohort of 480 patients with inherited retinal diseases (IRDs), we identified seven patients with mutations in IMPG1 or IMPG2. Multimodal imaging was performed to assess the clinical phenotypes, including fundus photography, fundus autofluorescence, fluorescein angiography, and spectral domain optical coherence tomography (SD-OCT). We provide structure modeling and analysis of each variant.

Results: Our findings indicate a prevalence of 1.45% of IRD patients being affected by IMPG mutations; two were diagnosed with RP and five with VMD. One VMD patient carried a novel IMPG1 p.Asp423Glu mutation. Most patients exhibited heterozygous mutations, and one RP patient presented a compound heterozygous mutation in IMPG2.

Conclusions: This work describes a novel mutation and expands our understanding of the specific IMPG protein domains implicated in RP and VMD. Furthermore, it establishes, for the first time, the prevalence of IMPG mutations in an IRD population.