Inherited retinal disease genes with dual inheritance patterns: insights from the IRD-PT registry.
Genes with both recessive and dominant inheritance caused 12% of inherited retinal disease diagnoses.
Inherited retinal disease genes with dual inheritance patterns: insights from the IRD-PT registry.
Inherited retinal diseases (inherited retinal diseases) typically follow a single inheritance pattern, but some genes cause disease through both autosomal recessive (autosomal recessive) and autosomal dominant (autosomal dominant) patterns, challenging genetic counselling.
This study aims to identify dual inheritance genes in a Portuguese cohort and characterise the prevalence of each inheritance mode and associated phenotypes.
Cross-sectional study at Portugal's largest inherited retinal diseases referral centre.
PRPH2 (95.0% autosomal dominant) was associated with retinitis pigmentosa (retinitis pigmentosa) and macular dystrophies.
ABCC6 (91.3% autosomal recessive) was linked to pseudoxanthoma elasticum (pseudoxanthoma elasticum).
BEST1 (91.7% autosomal dominant) mainly caused Best disease, while PROM1 (76.9% autosomal recessive) was linked to retinitis pigmentosa, macular dystrophy and cone-rod dystrophy.
PRPF31 (88.9% autosomal dominant) was exclusively associated with retinitis pigmentosa.
Dual inheritance genes accounted for 12% of our genetic diagnoses. This spectrum, modulated by variant location and allele dosage, determines phenotypes and contributes to inherited retinal diseases heterogeneity.
Deep phenotyping and comprehensive molecular diagnosis are essential for accurate genetic counselling and patient management.