New genotype-phenotype correlations and management recommendations for individuals with RERE variants - PubMed
2 hours ago
- #genotype-phenotype correlations
- #RERE variants
- #neurodevelopmental disorders
- The study assembled 54 individuals with RERE variants, including 30 new cases, to define phenotypic spectrum and correlations.
- Individuals were grouped by variant type: loss-of-function, missense inside/outside a histidine-rich region (HRR), and HRR in-frame deletions/duplications.
- Developmental delay, intellectual disability, and/or autism were common across all groups.
- Loss-of-function variants linked to fewer multisystem anomalies and higher likelihood of inheritance from mildly symptomatic/asymptomatic parents.
- HRR-associated missense variants and in-frame duplications were associated with more multisystem phenotypes and usually arise de novo.
- Protein modeling indicated that HRR missense variants are structurally stabilizing, suggesting gain-of-function or dominant-negative mechanisms.
- Findings expand the clinical spectrum, refine genotype-phenotype correlations, and support variant-specific management and genetic counseling approaches.