Mutations in IMPG1 cause autosomal dominant and recessive retinitis pigmentosa

Abstract

Purpose : To identify the causative mutation in a large family with autosomal dominant retinitis pigmentosa (adRP) and consequently to genetically characterize a cohort of RP patients without mutation in known genes.

Methods : A large adRP family without mutation in the known RP genes was screened for mutations using whole-exome sequenging (WES). Following the identification of an IMPG1 mutation, additional dominant and recessive RP probands were screened for mutation in this gene by targeted next-generation sequencing (tNGS). Clinical investigations included visual acuity and visual field testing, fundus examination, high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence imaging, full-fields and multifocal electroretinogram (ERG) recording.

Results : By WES, a heterozygous splicing mutation in the IMPG1 gene, c.1824+1G>A was identified in a large family with adRP. Three more families with different novel missense mutations were identified. All the variants segregated with the disease phenotype and are predicted to be pathogenic.

Conclusions : We identified a novel causative gene, IMPG1, responsible for autosomal dominant and recessive retinitis pigmentosa (RP). IMPG1 was previously associated with vitelliform macular dystrophy (VMD). In conclusion, mutations in the same gene can lead to two clinical entities, RP and VMD as it was reported previously for IMPG2, paralog gene of IMPG1.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.