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Researchers Uncover Genetic Cause For Kidney Disease Linked To Children

Mon, 21 Dec 2009 13:43:5

Ayinde O. Chase - AHN Editor

Boston, MA, USA (AHN) - Researchers from Children's Hospital Boston and Brigham and Women's Hospital have identified an important genetic cause of a devastating kidney disease that is the second leading cause of kidney failure in children.

The study may provide clues to developing treatments for the disease, focal segmental glomerulosclerosis (FSGS), which currently forces children and young adults onto dialysis and often requires a kidney transplant.

Patients with FSGS are often treated with steroids, which are only partially effective and have very harsh side effects. In addition, they often face several trips a week to the hospital for dialysis, and many require a kidney transplant, along with lifelong treatment with powerful immunosuppressants to prevent organ rejection.

The research team, led by Elizabeth Brown, MD, of Children's Division of Nephrology, working in the laboratory of Martin Pollak, MD, of the Renal Division at Brigham and Women's Hospital, identified the gene by performing a genetic linkage analysis in two large families with FSGS. Linkage analysis is a gene-finding technique that compares affected with unaffected family members, looking for a piece of DNA whose location is already known, and that is inherited only by affected members.

Researchers honed in on a region of chromosome 14q. By sequencing multiple genes in this region, they detected nine different mutations, all of them in a gene called INF2. They then sequenced INF2 in 91 additional families. In all, they found INF2 mutations in 11 of 93 families.

There have been a few descriptions of other genes that result in FSGS, but Brown and colleagues think INF2 is an important find. Mutations on this gene seem to affect larger numbers of families than those on previously discovered genes, and may be more relevant in understanding how the disease originates physiologically.

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