Elucidation of the mechanisms of hyperuricemia in patients with familial juvenile hyperuricemic nephropathy will shed light on the function of uromodulin, functional impairment of which eventually results in diminished uric acid excretion.
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.
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.
However, UMOD, REN or HNF-1β mutations are found in only approximately 45% of FJHN probands, indicating the involvement of other genetic loci in approximately 55% of probands.
In a large Belgian family with FJHN, a tight linkage between the disorder and the marker D16S3060, located within the MCKD2 locus on chromosome 16p12 (maximal two-point logarithmic odds score of 3.74 at a recombination fraction of theta = 0), was observed in this study.
In contrast, recently, another group described mutations in the UMOD gene as responsible for MCKD2 and familial juvenile hyperuricemic nephropathy (FJHN).
Multiple names have been proposed for these disorders, including 'Medullary Cystic Kidney Disease (MCKD) type 2', 'Familial Juvenile Hyperuricemic Nephropathy (FJHN)', or 'Uromodulin-Associated Kidney Disease (UAKD)' for UMOD-related diseases and 'MCKD type 1' for the disease caused by MUC1 mutations.
Multiple names have been proposed for these disorders, including 'Medullary Cystic Kidney Disease (MCKD) type 2', 'Familial Juvenile Hyperuricemic Nephropathy (FJHN)', or 'Uromodulin-Associated Kidney Disease (UAKD)' for UMOD-related diseases and 'MCKD type 1' for the disease caused by MUC1 mutations.
Our observations support the hypothesis that ER accumulation of mutant uromodulin may cause ER stress, providing a potential mechanism for the progression of UMOD-related kidney disease.
Our results suggested that the novel uromodulin mutations found in the Chinese families lead to misfolded protein, which was retained in the endoplasmic reticulum, finally contributed to the phenotype of FJHN.
Our results suggested that the novel uromodulin mutations found in the Chinese families lead to misfolded protein, which was retained in the endoplasmic reticulum, finally contributed to the phenotype of FJHN.