biostudies-literatureBiswas PNEI NIH HHSResearch to Prevent BlindnessNCI NIH HHS189-199https://www.ebi.ac.uk/biostudies/studies/S-EPMC7878419biostudies-literatureUnknown42(2)Inherited retinal degenerations (IRDs) are a group of genetically heterogeneous conditions with a broad phenotypic heterogeneity. Here, we report detection and validation of the underlying cause of progressive retinal degeneration in a nuclear family of European descent with a single affected individual. Whole genome sequencing of the proband and her unaffected sibling identified a novel intron 8 donor splice site variant (c.1296 + 1G>A) and a novel 731 base pair deletion encompassing exon 9 (Chr2:g.112751488_112752218 del) resulting in c.1297_1451del; p.K433_G484fsTer3 in the Mer tyrosine kinase protooncogene (MERTK), which is highly expressed in the retinal pigment epithelium (RPE). The proband carried both variants in the heterozygous state, which segregated with disease in the pedigreeHuman mutationDetection and validation of novel mutations in MERTK in a simplex case of retinal degeneration using WGS and hiPSC-RPEs model.PMC7878419R00 EY024648T32 EY026590R01 EY021237R01 EY030591T32 CA067754P30 EY022589Raghavendra PBVoronchikhina MFerreyra HZawaydeh QWahlin KRiazuddin SAMatsui HAyyagari RBiswas PBorooah SZhou JFrazer KAfalseDetection and validation of novel mutations in MERTK in a simplex case of retinal degeneration using WGS and hiPSC-RPEs model.Inherited retinal degenerations (IRDs) are a group of genetically heterogeneous conditions with a broad phenotypic heterogeneity. Here, we report detection and validation of the underlying cause of progressive retinal degeneration in a nuclear family of European descent with a single affected individual. Whole genome sequencing of the proband and her unaffected sibling identified a novel intron 8 donor splice site variant (c.1296 + 1G>A) and a novel 731 base pair deletion encompassing exon 9 (Chr2:g.112751488_112752218 del) resulting in c.1297_1451del; p.K433_G484fsTer3 in the Mer tyrosine kinase protooncogene (MERTK), which is highly expressed in the retinal pigment epithelium (RPE). The proband carried both variants in the heterozygous state, which segregated with disease in the pedigree2021-01-01T00:00:00Z2021 Feb2026-04-29T10:10:54.497Z2022-02-11T15:44:01.989ZS-EPMC78784193325216710.1002/humu.24146