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Inherited retinal disease genes with dual inheritance patterns: insights from the IRD-PT registry
Mariana Ferreira Francisco1,2, Beatriz Gaspar1,2, Rufino Silva1,2,3
1Ophthalmology Department, Hospitais da Universidade de Coimbra (HUC), Unidade Local de Saúde de Coimbra, Coimbra, Portugal.
Journal of Medical Genetics
|June 19, 2026
Summary
Some inherited retinal diseases (IRDs) can be caused by genes with both autosomal recessive (AR) and autosomal dominant (AD) inheritance patterns. This study identified nine such dual inheritance genes in a Portuguese cohort, impacting genetic diagnosis and counselling for IRDs.
Area of Science:
- Ophthalmology and Genetics
- Molecular Biology and Genetic Diseases
Background:
- Inherited retinal diseases (IRDs) often follow a single inheritance pattern (autosomal recessive or autosomal dominant).
- Certain genes causing IRDs exhibit dual inheritance patterns, complicating genetic diagnosis and counselling.
- Understanding these dual inheritance genes is crucial for accurate patient management.
Purpose of the Study:
- To identify genes responsible for IRDs through both autosomal recessive (AR) and autosomal dominant (AD) inheritance patterns within a Portuguese cohort.
- To determine the prevalence of each inheritance mode for identified dual-inheritance genes.
- To characterize the phenotypes associated with these dual-inheritance genes and establish genotype-phenotype correlations.
Main Methods:
- A cross-sectional study was conducted at Portugal's largest IRD referral center.
- Literature review identified genes with known dual inheritance patterns.
- The IRD-PT registry was screened for these genes, with AR vs. AD proportions calculated and clinical features analyzed for genotype-phenotype correlations.
Main Results:
- Nine out of 40 dual-inheritance genes screened were found in the IRD-PT registry, affecting 102 families (141 patients).
- Specific genes like PRPH2 (95% AD), ABCC6 (91.3% AR), BEST1 (91.7% AD), and PROM1 (76.9% AR) were associated with distinct IRD phenotypes such as retinitis pigmentosa, macular dystrophies, and pseudoxanthoma elasticum.
- Other identified genes included PRPF31, IMPG2, IMPG1, NR2E3, and RP1, each linked to specific retinal conditions and inheritance patterns.
Conclusions:
- Dual inheritance genes represent 12% of genetic diagnoses in this cohort, highlighting their significance in IRD heterogeneity.
- Phenotype expression is influenced by variant location and allele dosage, underscoring the complexity of these genetic conditions.
- Comprehensive molecular diagnosis and deep phenotyping are essential for effective genetic counselling and management of patients with IRDs.
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