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ABSTRACT: Background
UMOD mutations cause familial juvenile hyperuricemic nephropathy (FJHN) and medullary cystic kidney disease (MCKD), although these phenotypes are nonspecific.Design, setting, participants, & measurements
We reviewed cases of UMOD mutations diagnosed in the genetic laboratories of Necker Hospital (Paris, France) and of Université Catholique de Louvain (Brussels, Belgium). We also analyzed patients with MCKD/FJHN but no UMOD mutation. To determine thresholds for hyperuricemia and uric-acid excretion fraction (UAEF) according to GFR, these parameters were analyzed in 1097 patients with various renal diseases and renal function levels.Results
Thirty-seven distinct UMOD mutations were found in 109 patients from 45 families, all in exon 4 or 5 except for three novel mutations in exon 8. Median renal survival was 54 years. The type of mutation had a modest effect on renal survival, and intrafamilial variability was high. Detailed data available in 70 patients showed renal cysts in 24 (34.3%) of nonspecific localization in most patients. Uricemia was >75th percentile in 31 (71.4%) of 42 patients not under dialysis or allopurinol therapy. UAEF (n = 27) was <75th percentile in 70.4%. Among 136 probands with MCKD/FJHN phenotype, UMOD mutation was found in 24 (17.8%). Phenotype was not accurately predictive of UMOD mutation. Six probands had HNF1B mutations.Conclusions
Hyperuricemia disproportionate to renal function represents the hallmark of renal disease caused by UMOD mutation. Renal survival is highly variable in patients with UMOD mutation. Our data also add novel insights into the interpretation of uricemia and UAEF in patients with chronic kidney diseases.
SUBMITTER: Bollee G
PROVIDER: S-EPMC3359549 | biostudies-literature | 2011 Oct
REPOSITORIES: biostudies-literature
Bollée Guillaume G Dahan Karin K Flamant Martin M Morinière Vincent V Pawtowski Audrey A Heidet Laurence L Lacombe Didier D Devuyst Olivier O Pirson Yves Y Antignac Corinne C Knebelmann Bertrand B
Clinical journal of the American Society of Nephrology : CJASN 20110825 10
<h4>Background</h4>UMOD mutations cause familial juvenile hyperuricemic nephropathy (FJHN) and medullary cystic kidney disease (MCKD), although these phenotypes are nonspecific.<h4>Design, setting, participants, & measurements</h4>We reviewed cases of UMOD mutations diagnosed in the genetic laboratories of Necker Hospital (Paris, France) and of Université Catholique de Louvain (Brussels, Belgium). We also analyzed patients with MCKD/FJHN but no UMOD mutation. To determine thresholds for hyperuri ...[more]