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New Genetic Cause Identified For Chronic Kidney Disease

A new single-gene cause of has been discovered that implicates a not previously believed to be related to the disease, according to new research from the University of Michigan.

The research was published in the journal Nature Genetics.

“In developed countries, the frequency of chronic kidney disease is continually increasing for unknown reasons. The disease is a major health burden,” says Friedhelm , M.D., the paper’s senior author and professor of pediatrics and of human genetics at C.S. Mott Children’s Hospital.

Using whole exome sequencing, Hildebrandt and his colleagues studied a model disorder for , , and detected a new single-gene cause of CKD that implicates a disease mechanism formerly not related to CKD – DNA damage response signaling (DDR).

“Since DNA damage is cause by a whole variety of chemical compounds it may now be important to see whether certain ‘genotoxins’ may play a role in the increase of CKD,” says Hildebrandt who is also an investigator for the Howard Hughes Medical Institute.

The researchers identified mutations of Fanconi anemia-associated nuclease 1 (FAN1) as causing karyomegalic interstitial nephritis (KIN) in patients with CKD. Depletion of fan1 in a zebrafish model of disease revealed increased DDR, apoptosis, and kidney cysts akin to nephronophthisis.

“Our findings implicate susceptibility to environmental genotoxins and inadequate DNA repair as novel mechanisms of renal fibrosis and CKD,” Hildebrandt said.

Source

Additional authors: Multiple authors include, from the University of Michigan: Weibin Zhou and as co-first authors, Department of Pediatrics; Joseph Washburn, Comprehensive Cancer Center.
Funding: National Institutes of Health; Burroughs Wellcome Fund Career Award for Medical Scientists; Doris Duke Charitable Distinguished Clinical Scientist Award; National Institute of Diabetes and Digestive and Kidney Diseases.
University of Michigan Health System