Dahan Karin, Fuchshuber Arno, Adamis Stavroula, Smaers Michèle, Kroiss Sabine, Loute Guy, Cosyns Jean-Pierre, Hildebrandt Friedhelm, Verellen-Dumoulin Christine, Pirson Yves
Center for Human Genetics, Catholic University of Louvain, Brussels, Belgium.
University Children's Hospital, Freiburg, Germany.
J Am Soc Nephrol. 2001 Nov;12(11):2348-2357. doi: 10.1681/ASN.V12112348.
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.
家族性青少年高尿酸血症肾病（FJHN）是一种常染色体显性疾病，在儿童期以高尿酸血症为先兆；其特征为慢性间质性肾炎，伴有肾小管基底膜明显增厚，并在成年期导致进行性肾衰竭。最近，两个捷克家族中的FJHN基因被定位于16号染色体p11.2，靠近MCKD2基因座，该基因座与在一个意大利家族中观察到的常染色体显性遗传性髓质囊性肾病的一个变体有关。在一个患有FJHN的比利时大家族中，本研究观察到该疾病与位于16号染色体p12上MCKD2基因座内的标记D16S3060之间存在紧密连锁（在重组率θ = 0时，最大两点对数优势分数为3.74）。候选区域进一步缩小至D16S501和D16S3036之间1.3兆碱基的区间。结合先前报道的2型髓质囊性肾病与比利时家族中出现的FJHN之间显著的临床和病理相似性（包括髓质囊肿的存在），本研究表明这两种疾病是同一疾病的不同方面。
