Hypomorphic IDUA genotypes are associated with retinitis pigmentosa in individuals without syndromic mucopolysaccharidosis type I.

Hypomorphic IDUA genotypes are linked to late-onset retinitis pigmentosa without systemic MPS I features in individuals aged 46-73 years.

• Why it matters: Understanding the genetic basis of isolated retinal disease can improve diagnosis and reveal broader phenotypic effects of IDUA variants beyond classic MPS I, addressing gaps in genotype-phenotype correlations.
• What they did: The study analyzed 14 individuals from 12 families with bi-allelic IDUA variants, using biochemical assays, functional cell-based expression platforms, and transcript analysis to assess enzyme activity and splicing effects.
• The result: Findings show residual enzyme activity in all cases, with most variants being hypomorphic, expanding the phenotypic spectrum of IDUA mutations to include late-onset retinal disease and emphasizing the importance of integrated genetic and functional testing.