IOB researchers discover new gene linked to retinitis pigmentosa
In a groundbreaking study published in The American Journal of Human Genetics, the research team led by Carlo Rivolta has identified a new gene associated with retinitis pigmentosa (RP). Genetically, RP is highly heterogeneous, with pathogenic variants identified in more than 100 genes so far.
Over the years, our understanding of the molecular genetics of RP has advanced significantly, mostly through the use of next-generation sequencing technologies. Yet, its missing heritability is still considerable, implying that a potentially high number of genes linked to inherited retinal diseases still awaits molecular identification.
Coenzyme Q10: a molecule essential for cellular energy production
Scientists at the Institute of Molecular and Clinical Ophthalmology Basel (IOB) now discovered that also mutations in the COQ8B gene can lead to non-syndromic RP. This finding is particularly intriguing because COQ8B is known to be involved in the production of coenzyme Q10 (CoQ10), a molecule essential for cellular energy production.
CoQ10 plays an essential role in mitochondrial oxidative phosphorylation and in cellular energy production. Primary coenzyme Q (CoQ) deficiencies include a collection of rare mitochondrial disorders, all with an autosomal-recessive pattern of inheritance, and due to genetic variants in elements of the CoQ biosynthetic pathway. These conditions are characterized by a very high clinical heterogeneity, likely reflecting the variable functions of the different proteins affected by disease-causing DNA changes. Primary clinical manifestations include neurologic, renal, cardiac, and ophthalmologic phenotypes. Interestingly, one of the phenotypes associated with defects in proteins of the CoQ10 biosynthetic pathway is retinopathy, reported in association with different gene variants in individuals with syndromic or non-syndromic RP.
"What is fascinating is that until now, COQ8B mutations were primarily associated with kidney disease. Our study reveals that certain mutations in this gene can cause retinal degeneration without affecting the kidneys," explains Rivolta.
The team identified five individuals from four families who had RP caused by different combinations of COQ8B mutations. Using advanced laboratory techniques, they demonstrated how these genetic changes impair the function of the COQ8B protein.
Coenzyme Q10 biosynthesis pathway still poorly understood
“This study will also help to better understand the significance of COQ8B in the coenzyme Q10 biosynthesis pathway, which is still poorly understood” says Ana Iglesias, lead author of the study.
This discovery does not only expand our understanding of the genetic causes of inherited retinal diseases but also opens up new possibilities for potential treatments. It suggests that supplements of coenzyme Q10 or related compounds could potentially help patients with this specific form of RP.
This work underscores the importance of comprehensive genetic testing in diagnosing inherited eye diseases and highlights the complex connections between cellular energy production and retinal health.
Source: IOB
Bi-allelic variants in COQ8B, a gene involved in the biosynthesis of coenzyme Q10, lead to non-syndromic retinitis pigmentosa
Iglesias-Romero, Ana Belén et al.; The American Journal of Human Genetics, Volume 111, Issue 10, 2299 - 2306