These polymorphisms affect uromodulin concentration in the urine, and lower genetically determined urinary uromodulin concentrations seem to protect against renal disease.
Autosomal dominant medullary cystic kidney disease type 2 (MCKD2) is a tubulo-in terstitial nephropathy that causes renal salt wasting, hyperuricemia, gout, and end-stage renal failure in the fifth decade of life.
These studies quantitatively show that the autosomal-dominant gene mutations responsible for UMOD-associated kidney disease cause a profound reduction of THP excretion.
These studies quantitatively show that the autosomal-dominant gene mutations responsible for UMOD-associated kidney disease cause a profound reduction of THP excretion.
Considering MCKD2 to be a distinct molecular entity, the analysis suggests that as many as three kidney disease genes may be located in close proximity on 16p11.2.
We postulate that mutation of UMOD disrupts the tertiary structure of UMOD and is responsible for the clinical changes of interstitial renal disease, polyuria, and hyperuricaemia found in MCKD2 and FJHN.