Mutation Linked to Hereditary Kidney Disease

A study has found that mutations in the uromodulin (UMOD) gene are linked to the development of two inherited kidney diseases, medullary cystic kidney disease 2 (MCKD2) and familial juvenile hyperuricemic nephropathy (FJHN). The study was published in the December 2002 issue of the Journal of Medical Genetics.

The UMOD gene ordinarily produces the protein uromodulin (Tamm-Horsfall protein), which is the most abundant protein in normal urine and a major component of tubular and urinary casts.

Investigators from Wake Forest University Baptist Medical Center (Winston-Salem, NC, US) and the University of Pittsburgh (PA, US) used genetic linkage and haplotype analyses to study two large, multigenerational families with mutations at the chromosome 16p FJHN gene locus. To permit refinement of the candidate interval and localization of candidate genes, an integrated physical and genetic map of the candidate region was developed. DNA sequencing of candidate genes was performed to detect mutations in subjects affected with FJHN (three unrelated families) and MCKD2 (one family).

The data accumulated during the study provided the first direct evidence that MCKD2 and FJHN arise from mutation of the UMOD gene and are allelic disorders. The authors postulated that mutation of UMOD disrupted the tertiary structure of UMOD and was responsible for the clinical changes of interstitial renal disease, polyuria, and hyperuricemia found in MCKD2 and FJHN.

"There had previously been a report speculating that these two conditions were in fact variations of the same disease,” explained senior author Dr. Anthony J. Bleyer, associate professor of internal medicine (nephrology) at Wake Forest University. "Our research has been able to prove that they are.”
Wake Forest University Baptist Medical Center >> www.wfu.edu



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