Multimorbidity due to novel pathogenic variants in theWFS1/RP1/NOD2genes: autosomal dominant congenital lamellar cataract, retinitis pigmentosa and Crohn’s disease in a British family

Abstract

BackgroundA five generation family has been analysed by whole exome sequencing (WES) for genetic associations with the multimorbidities of congenital cataract (CC), retinitis pigmentosa (RP) and Crohn’s disease (CD).MethodsWES was performed for unaffected and affected individuals within the family pedigree followed by bioinformatic analyses of these data to identify disease-causing variants with damaging pathogenicity scores.ResultsA novel pathogenic missense variant inWFS1: c.1897G>C; p.V633L, a novel pathogenic nonsense variant inRP1: c.6344T>G; p.L2115* and a predicted pathogenic missense variant inNOD2: c.2104C>T; p.R702W are reported. The three variants cosegregated with the phenotypic combinations of autosomal dominant CC, RP and CD within individual family members.ConclusionsHere, we report multimorbidity in a family pedigree listed on a CC register, which broadens the spectrum of potential cataract associated genes to include bothRP1andNOD2.