Inherited retinal disease genes with dual inheritance patterns: insights from the IRD-PT registry

IRD genes causing disease through two inheritance modes (AR and AD) depending on variant location and allelic dosage

A cross-sectional study at Portugal's largest IRD referral center identified, among 40 reported dual-inheritance genes, 9 showing both patterns in the IRD-PT registry (102 families, 141 patients). PRPH2 (95% AD) was associated with retinitis pigmentosa and macular dystrophies, ABCC6 (91% AR) with pseudoxanthoma elasticum, and BEST1 (91% AD) with Best disease. Genotype-phenotype correlations were modulated by variant location and allelic dosage. These dual-inheritance genes accounted for 12% of the registry's genetic diagnoses.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Genetic counseling for IRDs is particularly complex for these dual-inheritance genes. This Portuguese registry illustrates how the same gene can have very different diagnostic implications depending on inheritance mode — a point often underestimated when interpreting IRD panels. The phenotypic completeness of the registry is a notable methodological strength.