Familial juvenile hyperuricemic nephropathy and autosomal dominant medullary cystic kidney disease type 2: two facets of the same disease?
Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant disorder heralded by hyperuricemia during childhood; it is characterized by chronic interstitial nephritis, with marked thickening of tubular basement membranes, and leads to progressive renal failure during adulthood. A gene for FJHN in two Czech families was recently mapped to chromosome 16p11.2, close to the MCKD2 locus, which is responsible for a variant of autosomal dominant medullary cystic kidney disease observed in an Italian family. 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. The candidate region was further narrowed to a 1.3-Mb interval between D16S501 and D16S3036. Together with the striking clinical and pathologic resemblance between previously reported medullary cystic kidney disease type 2 and FJHN occurring in the Belgian family (including the presence of medullary cysts), this study suggests that these two disorders are facets of the same disease.
Dahan
Karin
K
Center for Human Genetics, Catholic University of Louvain, Brussels, Belgium.
Fuchshuber
Arno
A
University Children's Hospital, Freiburg, Germany.
Adamis
Stavroula
S
Center for Human Genetics, Catholic University of Louvain, Brussels, Belgium.
Smaers
Michèle
M
Center for Human Genetics, Catholic University of Louvain, Brussels, Belgium.
Kroiss
Sabine
S
University Children's Hospital, Freiburg, Germany.
Loute
Guy
G
Department of Nephrology, Princesse Paola Hospital, Aye, Belgium.
Cosyns
Jean-Pierre
JP
Department of Pathology, Catholic University of Louvain, Brussels, Belgium.
Hildebrandt
Friedhelm
F
University Children's Hospital, Freiburg, Germany.
Verellen-Dumoulin
Christine
C
Center for Human Genetics, Catholic University of Louvain, Brussels, Belgium.
Pirson
Yves
Y
Division of Nephrology, Catholic University of Louvain, Brussels, Belgium.
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D003560:Cysts / Q000235:genetics* / Q000473:pathology; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000145:classification / Q000235:genetics* / Q000473:pathology / Q000652:urine*; D007679:Kidney Medulla / Q000473:pathology; D008297:Male; D010375:Pedigree; D014527:Uric Acid / Q000097:blood*
D014527:Uric Acid