These observations suggest that there are different urinary and plasma uromodulin profiles in early and late disease and that there may be an altered direction of uromodulin secretion in the course of FJHN as a result of improper intracellular sorting of the mutated protein in the thick ascending limb.
Furthermore, the genetic basis of familial juvenile hyperuricemic nephropathy (FJHN), glomerulocystic kidney disease (GCKD) and autosomal dominant medullary cystic kidney disease 2 (MCKD2) has been recently attributed to mutations within the THP gene.
Medullary cystic kidney disease type 2 (also known as uromodulin-associated kidney disease) likely represents a form of endoplasmic reticulum storage disease, with deposition of the abnormal uromodulin protein in the endoplasmic reticulum, leading to tubular cell atrophy and death.
FJHN and MCKD2 are allelic, result from uromodulin (UMOD) mutations and the term uromodulin-associated kidney disease (UAKD) has been proposed for them.
Recent reports on the discovery of mutations of the uromodulin (UMOD) gene in families with FJHN encouraged us to screen UMOD mutations in Japanese families with FJHN, including family 1.
A mutation in the uromodulin gene (16p11-13) has recently been linked to medullary cystic kidney disease type 2 and familial juvenile hyperuricemic nephropathy.
The disease complex medullary cystic disease/familial juvenile hyperuricemic nephropathy (MCKD/FJHN) is characterized by alteration of urinary concentrating ability, frequent hyperuricemia, tubulo-interstitial fibrosis, cysts at the cortico-medullary junction and renal failure.
In contrast, recently, another group described mutations in the UMOD gene as responsible for MCKD2 and familial juvenile hyperuricemic nephropathy (FJHN).
The clinical characteristics were similar to those of other patients suffering from uromodulin mutations and to those of patients suffering from medullary cystic kidney disease type 2 and familial juvenile hyperuricemic nephropathy.
The clinical characteristics were similar to those of other patients suffering from uromodulin mutations and to those of patients suffering from medullary cystic kidney disease type 2 and familial juvenile hyperuricemic nephropathy.