Gene link to inherited blindness discovered
- Some people with retinitis pigmentosa may actually have an extremely mild form of a metabolic disease that has gone unrecognised for decades.
- The childhood metabolic illness can also cause a form of inherited blindness in adults,
- International study co-led by scientists at the University of Manchester,
Faults in a gene known for causing a devastating childhood metabolic illness can also cause a form of inherited blindness in adults, an international study co-led by scientists at the University of Manchester, University College London and the Greenwood Genetic Center in the US has found.
In the first study of its kind, published in , the scientists show how changes in this gene can cause a much milder disease than previously known
They identified that in 14 patients with retinitis pigmentosa, it was caused by certain combinations of faults in a gene called IDUA.
The gene is normally associated with mucopolysaccharidosis type I (MPS I), a rare disorder that can cause severe physical disability, heart problems, skeletal abnormalities and shortened life expectancy.
Yet several of the patients in the study showed no signs of the disorder despite detailed medical assessments and follow-up into their forties, fifties, sixties and seventies.
Their failing eyesight was the first and sometimes only clue to an underlying health problem.
The findings suggest some people with retinitis pigmentosa may actually have an extremely mild form of a metabolic disease that has gone unrecognised for decades.
This study shows that the same gene can cause dramatically different disease outcomes, depending on how much of its related enzyme activity remains
The discovery expands our understanding of MPS I and reveals that the condition can exist in a much milder form than previously thought.
None of the patients carried the combinations of severe genetic faults normally seen in classic MPS I.
Instead, they carried milder combinations of gene faults in IDUA.
Through a series of lab experiments, the scientists found these milder faults act in different ways - some directly reducing the enzyme's activity, others disrupting the gene's splicing instructions - but in each case leaving behind only a tiny fraction, as little as 0.5 to 2 per cent, of normal function.
The scientists suspect this tiny amount of residual activity may be enough to protect most organs from damage while leaving the retina vulnerable.
One theory is that the eye may be especially sensitive to defects in the body's cellular recycling machinery because of its exceptionally high energy demands.
The findings could have implications for genetic screening programmes designed to identify rare diseases, including MPS I, in newborn babies.
And they also underline the importance of including IDUA and related metabolic genes in genetic testing for inherited retinal diseases.
Lead author from The University of Manchester said: "This study shows that the same gene can cause dramatically different disease outcomes, depending on how much of its related enzyme activity remains.
鈥淚n some patients we found almost no evidence of the devastating multisystem disorder typically associated with IDUA - their disease appeared confined to the retina, the mildest presentation we've seen to date.
鈥淭hese findings broaden the recognised spectrum of disease, improve diagnosis for patients with inherited blindness, and provide important clues about why the retina appears especially susceptible to even very small reductions in enzyme function.
鈥淲e hope they will help clinicians identify hitherto unrecognised cases of IDUA-related disease and pave the way for future treatments aimed at preserving vision before irreversible damage occurs.鈥�
- The paper Hypomorphic IDUA genotypes are associated with retinitis pigmentosa in individuals without syndromic mucopolysaccharidosis type I , published in ,听 is available at DOI: 10.1016/j.ajhg.2026.09.008