Gene Linked to Rare Metabolic Disorder also Associated with RP

October 30, 2013

After genetically screening an ethnically diverse group of 769 people with retinitis pigmentosa (RP), a Dutch research team found that three individuals’ disease was caused by defects in the gene MVK, which is also linked to a rare, sometimes severe, syndrome known as mevalonate kinase deficiency (MKD). However, these three people had only very mild MKD symptoms. Results of the study were published in the journal Ophthalmology.

Rob Collin
, Ph.D., the study’s lead investigator, at Radboud University Medical Centre, Nijmegen, the Netherlands, says that diverging disorders, ranging in severity, can arise from mutations in MVK. The gene encodes an enzyme involved in the production of metabolic substances required for normal development, reproduction and digestion.

Some MVK mutations lead to a severe form of MKD, which is characterized by significant physical deformities, problems with movement and balance and mortality before adulthood. Other mutations lead to a milder form of MKD in which episodes of fever are the most common symptom. MKD has been diagnosed in about 300 people worldwide.

“This study shows that the severity of a disease or syndrome is strongly correlated with the type of mutation affecting the function of a gene,” says Stephen Rose, Ph.D., the Foundation Fighting Blindness’ chief research officer. “In some cases, a mutation in a given gene may lead to one symptom such as RP. However, other mutations in the same gene may lead to a syndromic condition affecting many parts of the body. Evidence also suggests that other genetic and environmental factors affect disease severity.”

“From what we currently know, the majority of patients with MKD have not been reported to have RP,” says Dr. Collin. “This doesn’t necessarily mean that no symptoms of RP are present in these patients — clinicians may just not have always looked for them. Also, in the most severe cases, lethality may occur before adulthood and the onset of RP.”

Dr. Collin says that evidence is emerging that genes in which mutations cause severe systemic disorders or certain syndromes may also be mutated in patients with non-syndromic RP or RP with only mild non-ocular abnormalities. Such is the case with not only MVK, but also the BBS1 gene in which mutations can cause Bardet-Biedl syndrome (BBS).

In addition to RP, BBS can cause several other physical and mental developmental problems, obesity and kidney disease. However, Dr. Collin’s colleagues published a paper last year in Archives of Ophthalmology reporting that mutations in BBS1 may lead to only RP or no disease at all.

When a Condition is More than a Retinal Disease,” a post on the Foundation’s Eye on the Cure blog, provides additional information about syndromic conditions.