Dong Hun Lee

A Case of Familial Juvenile Hyperuricemic Nephropathy with Novel Uromodulin Gene Mutation, a Novel Heterozygous Missense Mutation in Korea

Familial Juvenile hyperuricemic nephropathy (FJHN, OMIM #162000) is a rare autosomal dominant disorder characterized by hyperuricemia with renal uric acid under-excretion, gout and chronic kidney disease. In most but not all families with FJHN, genetic studies have revealed mutations in the uromodulin (UMOD) gene located on chromosome 16p11-p13. We here described a novel heterozygous missense mutation (c.1382C>A causing p.Ala461Glu) in an affected 16-year-old male with hyperuricemia, gout and chronic kidney disease. His father was also affected and the UMOD mutation was found to segregate with the disease. There has been only one case report of Korean family with FJHN, which has not been diagnosed by genetic study. This is the first report of genetically diagnosed FJHN in Korea.

Lysophosphatidylcholine, Oxidized Low-Density Lipoprotein and Cardiovascular Disease in Korean Hemodialysis Patients: Analysis at 5 Years of Follow-up

Although oxidized low-density lipoprotein (LDL) and lysophosphatidylcholine (LPC) have been proposed as important mediators of the atherosclerosis, the long-term contribution to the risk of cardiovascular disease (CVD) in hemodialysis patients has not been evaluated. This study investigated the relation between oxidized LDL and LPC levels with long term risk of CVD. Plasma oxidized LDL and LPC levels were determined in 69 Korean hemodialysis patients as a prospective observational study for 5 yr. During the observation period, 18 cardiovascular events (26.1%) occurred including 6 deaths among the hemodialysis patients. The low LPC level group (≤ 254 µM/L, median value) had much more increased risk of CVD compared to the high LPC level group (> 254 µM/L) (P = 0.01). However, serum levels of oxidized LDL were not significantly different between groups with and without CVD. In adjusted Cox analysis, previous CVD, (hazard ratio [HR], 5.68; 95% confidence interval [CI], 1.94-16.63, P = 0.002) and low LPC level (HR, 3.45; 95% CI, 1.04-11.42, P = 0.04) were significant independent risk factors for development of CVD. It is suggested that low LPC, but not oxidized LDL, is associated with increased risk of CVD among a group of Korean hemodialysis patients.

Familial Juvenile Hyperuricemic Nephropathy and Uromodulin Gene Mutation

by hyperuricemia and slowly progressive chronic kidney disease. Therefore, the conditions caused by mutations in the gene encoding UMOD are preferentially called as uromodulin-associated kidney disease. Although FJHN is mostly caused by mutations of UMOD gene (FJHN1, OMIM 162000), it is genetically heterogeneous. Mutations in UMOD gene occur in only 40% of probands. 11) Re cently, mutations of different genes have been reported in a few families with FJHN: renin (REN) and hepatocyte nuclear factor-1 beta (HNF1B) on chromosomes 1q32.1 13) and 17q12, respectively. Mutations in REN gene were found to be responsible for a similar presentation; family history of gout and childhood anemia (FJHN2, OMIM 613092). 13) Mutations in HNF1B genes together account for 2.5% of FHJN. Mutations in other, as yet unidentified genes, may also account for some cases. Recent discovery of UMOD genetic variants as a cause of FJHN led a new concept. We previously reported a Korean family with Familial Juvenile Hyperuricemic Nephropathy and Uromodulin Gene Mutation