Multimorbidity due to novel pathogenic variants in the WFS1/RP1/NOD2 genes: autosomal dominant congenital lamellar cataract, retinitis pigmentosa and Crohn’s disease in a British family

Whole genome sequencing has allowed the medical community to learn more about disease inheritance patterns on a genetic and molecular level, and discover possible cases of digenic or trigenic inheritance patterns. Trigenic inheritance means that the phenotype - the observable characteristics - of a disease, is caused by the interaction of three genes. Digenic inheritance is when the interaction of two genes results in the phenotype. In this study, researchers analyzed five generations of a British family, conducting whole genome sequencing on individuals who were either affected or unaffected by the combination of congenital cataracts (CC), retinitis pigmentosa (RP), and Crohn’s Disease (CD). This method of conducting whole genome sequencing on multiple generations of a family found novel mutations on three genes - WFS1, RP1, and NOD2 - in all family members with the combination of CC, RP, and CD which provided insight into the relationship between these genes. This emphasizes the importance of identifying and understanding multimorbidities, or the coexistence of multiple chronic conditions or diseases.

What this means for Usher syndrome: This paper references an Usher syndrome-specific trigenic inheritance pattern of ADH5/ALDH2/ADGRV1, which highlights the significance of conducting this kind of study with more Usher syndrome genes.

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