Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In man, there are at least four isoforms of adenosine monophosphate deaminase (AMPD): myoadenylate deaminase in skeletal muscle, the L isoform in liver, and the E1 and E2 isoforms in erythrocytes. Myoadenylate deaminase is encoded by the AMPD1 gene located on chromosome 1 p13-p21, the L isoform by the AMPD2 gene, and both isoforms in erythrocytes by the AMPD3 gene. Myoadenylate deaminase deficiency is found in 2-3% of all muscle biopsies. The inborn type of myoadenylate deaminase deficiency is caused by a single mutant allele harbouring two mutations: C34-->T (Gln-->Stop) and C143-->T (Pro-48-->Leu). Population studies revealed a frequency of the mutant allele of 0.12 in Caucasian Americans and Germans. The C34-->T mutation is located in exon 2, which is alternatively spliced in part of the AMPD1 transcript in human muscle. Since the second mutation does not affect enzyme function, alternatively spliced mRNA encodes a catalytically active enzyme. Only one patient with a disorder linked to liver AMPD has been described so far. In this patient the decreased inhibition of this enzyme by GTP resulted in uric acid overproduction and gout. A complete lack of erythroyte AMPD activity is found in asymptomatic subjects. The molecular basis of both disorders is not yet known.
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PMID:Molecular biology of AMP deaminase deficiency. 803 42

Gout, which is commonly associated with hyperuricemia, affects 0.2% of the population. Hyperuricemia has a heterogeneous etiology that may be due to either over production and/or reduced renal clearance, of urate. In order to identify the mechanisms underlying reduced excretion of urate, we undertook positional cloning studies of familial juvenile hyperuricaemic nephropathy (FJHN), which is an autosomal dominant disorder characterized by hyperuricaemia, a low fractional renal excretion of urate, and chronic renal failure that is associated with interstitial fibrosis. The FJHN locus has been previously localized to a 22 centiMorgan interval flanked centromerically by D16S401 and telomerically by D16S3069, on chromosome 16p11-p13. This interval contains over 120 genes and we selected 13 renal expressed sequences to search for mutations in 5 unrelated FJHN families that contained 21 affected and 24 unaffected members. This revealed 5 heterozygous missense mutations (Cys77Tyr, Cys126Arg, Asn128Ser, Cys255Tyr and Cys300Gly) that altered evolutionary conserved residues in the gene encoding UROMODULIN. UROMODULIN, which is an 85 Kda glycoprotein, has roles in renal stone formation, the modulation of immune responses, and urothelial cytoprotection. The results of our studies, which have identified the gene causing FJHN, now indicate a further, novel role for UROMODULIN in urate metabolism.
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PMID:UROMODULIN mutations cause familial juvenile hyperuricemic nephropathy. 1262 36

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.
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PMID:A case of familial juvenile hyperuricemic nephropathy with novel uromodulin gene mutation, a novel heterozygous missense mutation in Korea. 2106 Jul 63