Three novel variants in the <i>UBAP1L</i> gene lead to a generalized retinal dystrophy

PURPOSE: In this study, we present three patients diagnosed with rod-cone and cone-rod dystrophy carrying likely biallelic variants in UBAP1L. METHODS: In this cross-sectional study, three participants underwent ophthalmological examinations and genetic testing. The clinical examination included best-corrected visual acuity, kinetic perimetry, ultrawidefield fundus autofluorescence and pseudocolor photography optical coherence tomography and electrophysiology. Genetic diagnostic testing was performed by in silico inherited retinal disease (IRD) gene panel testing based on genome sequencing. RESULTS: Participant A showed a rod-cone dystrophy phenotype with myopia and a relatively late disease onset in the fourth decade. Participants B and C showed a cone-rod dystrophy phenotype. Genetic diagnostic testing revealed two heterozygous variants in UBAP1L in participant A, namely a 1 bp deletion c.566del, p.Ser189ThrfsTer80 and a variant in the consensus splice region c.910-7 G > A, p.?, an apparent homozygous 1 bp deletion c.472del, p.Ala158ArgfsTer27 in participant B, and a homozygous canonical splice-site variant c.120 + 1 G > T, p.? in participant C. CONCLUSIONS: Three novel disease-associated variants and one previously reported variant in the UBAP1L gene were identified as the likely cause of rod-cone dystrophy and cone-rod dystrophy phenotypes. The identification of additional cases, together with detailed phenotypic characterization and longitudinal follow-up, will enable clearer genotype-phenotype correlations in the future.