Copy number variation found to cause rare kidney disease
A rare form of kidney disease linked to a genetic mutation in the innate immune system has been identified by researchers funded by the Wellcome Trust and the Medical Research Council.
So far, the disease, which the researchers have named CFHR5 nephropathy, has been identified in over 100 people, all of whom are of Cypriot descent, including some living in the UK. Symptoms include blood in the urine - both microscopic and, occasionally, visible - and progressive kidney malfunction.
Under current guidelines, the presence of blood in the urine - when not accompanied by traces of protein, urinary tract abnormalities or impairment to the kidneys - is considered benign and is not investigated further. However, in a study published today in 'The Lancet', researchers from Imperial College London and University College London (UCL) show that in rare cases, it can be a symptom of this progressive, chronic kidney disease.
Working with colleagues in Cyprus, the researchers identified an inherited kidney disorder caused by a copy number variation of the gene CFHR5. Copy number variations are large chunks of DNA either duplicated or deleted from our genes when passed down to children. CFHR5 is involved in the production of proteins used by the complement system, a key component of the body's innate immune response.
The mutation was found in 26 individuals from 11 families. All were of Cypriot ancestry. The researchers believe the mutation dates back to a single common ancestor over 16 generations ago.
"We believe this mutation accounts for a significant proportion of kidney disease in the Cypriot population, both on the island itself and worldwide," says Dr Matthew Pickering, a Wellcome Trust Senior Fellow at Imperial College London. "It is a potentially serious disease, but easily detectable from a simple DNA or blood test."
Although scientists do not yet fully understand how the mutation leads to disease, the researchers believe that the findings should help them provide effective genetic counselling to families affected by the condition.
"People who carry just one copy of the genetic mutation will almost certainly develop the condition," says Professor Patrick Maxwell from UCL. "Now that we know the mutation responsible, we are in a position to offer genetic counselling to parents considering having children."
No evidence-based treatments currently exist for the condition, so the researchers are now focusing their research efforts on the development of therapies for CFHR5 nephropathy.
Reference
Gale DP et al. Complement Factor H-Related protein 5 (CFHR5) Nephropathy: an endemic cause of renal disease in Cyprus. The Lancet; 26 Aug 2010.
About Medical Research Council
For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including the first antibiotic penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century.
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About the Wellcome Trust
The Wellcome Trust is a global charity dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests.