Gene Mutation Plays a Major Role in Inherited Kidney Disease


A condition known as focal segmental glomerulosclerosis (FSGS) causes about 10-15% of all cases of nephrotic syndrome, a group of symptoms that damage the kidneys, leading to chronic kidney disease. Researchers from Children’s Hospital in Boston have found that a mutation in a gene called INF2 is the most common cause of FSGS. Approximately 20,000 persons are currently living with kidney failure due to FSGS in the United States.

Focal Segmental Glomerulosclerosis Hampers Filtering, Damaging Kidneys

FSGS is scar tissue that forms in a part of the kidney called the glomeruli. The glomeruli serve as filters, helping to rid the body of unnecessary or harmful substances. A person with FSGS has impaired filtering through the kidneys, leading to irreparable damage. More than half of patients with focal segmental glomerulosclerosis develop chronic kidney failure within 10 years.

Recent studies have shown that the incidence of FSGS is increasing and it is the second leading cause of kidney failure in children. Men and boys are affected slightly more than females, and it also occurs more frequently in African-Americans.

Read: Chronic Kidney Disease Rises


During the last decade, several genes that are mutated in patients with hereditary FSGS have been identified, including INF2 which produces a protein that helps maintain the structure of specialized kidney cells called podocytes. Podocytes are epithelial cells in the renal glomerulus that are key to filtering waste.

In a study of 54 families (78 patients) with a history of autosomal dominant FSGS, INF2 mutations were found in 17%. These mutations were located in one particular region of the gene that corresponds to an interaction with podocyte proteins.

Read: Lower Phosphorus Levels in Kidney Disease Patients Eating Vegetarian Diet

The findings might shed light on the mechanism behind INF2’s involvement in the development of FSGS and could be helpful as researchers design drugs to prevent or treat the disease.

Source References:
Olivia Boyer, Geneviève Benoit, et al. Mutations in INF2 Are a Major Cause of Autosomal Dominant Focal Segmental Glomerulosclerosis, JASN ASN.2010050518; published ahead of print January 21, 2011,doi:10.1681/ASN.2010050518

Brown EJ, Schlöndorff JS, et al. Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis. Renal Division, Children's Hospital, Boston, Massachusetts, USA. Nat Genet. 2010 Jan;42(1):72-6. Epub 2009 Dec 20. Erratum in: Nat Genet. 2010 Apr;42(4):361.