Familial juvenile hyperuricemic nephropathy: Detection of mutations in the uromodulin gene in five Japanese families

Kudo, Eiji; Kamatani, Naoyuki; Tezuka, Osamu; Taniguchi, Atsuo; Yamanaka, Hisashi; Yabe, Sachiko; Osabe, Dai; Shinohara, Syuichi; Nomura, Kyoko; Segawa, Masaya; Miyamoto, Tatsuro; Moritani, Maki; Kunika, Kiyoshi; Itakura, Mitsuo

doi:10.1111/j.1523-1755.2004.00559.x

Cited by 56 publications

(43 citation statements)

References 51 publications

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“…Hart et al [2] first identified that the mutation of the uromodulin (UMOD) gene is responsible for FJHN. FJHN is genetically heterogeneous and mostly caused by mutations in the UMOD gene located on chromosome 16p12.3-p13.11 [3,4,5]. …”

Section: Introductionmentioning

confidence: 99%

Novel Uromodulin Mutation in Familial Juvenile Hyperuricemic Nephropathy

Wei

Yang

et al. 2012

Am J Nephrol

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Background: Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant disorder characterized by early onset of hyperuricemia, decreased fractional renal urate excretion and progressive interstitial nephropathy. Mutations in the uromodulin (UMOD) gene encoding uromodulin/Tamm-Horsfall, a glycosylphosphatidylinositol (GPI)-anchored protein, cause this disease. Methods: One Chinese family with 13 FJHN-affected individuals is described. Clinical data, blood and urine samples of 7 affected members (all alive patients in this family) and 15 unaffected members were collected. Mutation analysis of the UMOD gene was performed by polymerase chain reaction and direct sequencing. Urinary uromodulin from affected or unaffected members of this family and healthy controls was examined by enzyme-linked immunosorbent assay kit. Expression of uromodulin in renal tissue was shown with immunofluorescence. Results: A novel mutation (p.T605G) within the uromodulin GPI anchor signal segment was identified in the affected individuals of this FJHN family. There was a markedly increased expression of uromodulin in renal tissue and significantly decreased urinary excretion of uromodulin in affected patients with an estimated glomerular filtration rate <60 ml/min/1.73 m². Conclusions: The present study reported a novel mutation in exon 9 of UMOD in the Chinese Han population, within the GPI anchor signal segment of uromodulin. Since the GPI anchor is linked with the release or secretion of proteins, our finding may provide further evidence for the underlying mechanism of decreased urinary excretion of uromodulin in FJHN.

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Section: Introductionmentioning

confidence: 99%

Novel Uromodulin Mutation in Familial Juvenile Hyperuricemic Nephropathy

Wei

Yang

et al. 2012

Am J Nephrol

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“…8 We have analyzed the 81 markers on chromosome 16p that are used in the analysis by Kudo et al 9 The pedigree consists of 65 individuals, but only 58 descendants are analyzed because seven ancestors have no effect on the maximization of the likelihood since their marker genotypes are not available (NA). We also changed the affected status of IV-21 to non-affected since Kudo et al 9 reported that it is a phenocopy. We assume that the mode of inheritance is autosomal dominant with one liability class with penetrance 0, 0.95 and 0.95.…”

Section: Pedigree Datamentioning

confidence: 99%

Exploration of the disease locus by a careful evaluation of the likelihood polynomial for pedigree data

Sugaya

Shibata

2011

J Hum Genet

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It is demonstrated through two case studies that a careful evaluation of the likelihood polynomial results in a more accurate localization of disease locus. The evaluation of the likelihood function as a polynomial enables more flexible exploration of the disease locus. Visualization by a contour plot of the function on a unit square of paternal and maternal recombination fractions along with a superimposed ellipsoid of the Fisher information matrix helps us to find a more accurate localization of the disease locus. Keywords: Fisher information; likelihood polynomial; pedigree analysis; sex-specific recombination fraction INTRODUCTIONThe aim of this paper is to demonstrate through two case studies that a careful evaluation of the likelihood polynomial yields a better result in a linkage analysis using pedigree data. A simple visualization of the likelihood on the whole region [0,1]Â[0,1] of paternal and maternal recombination fractions helps us understand more accurately what the pedigree data tell us about the disease locus. Superimposing the Fisher information matrix to the contour plot also helps us to see the reliability of the estimates of the fractions. We will use the probability inheritance algorithm 1 to evaluate the likelihood as a polynomial of recombination fractions:

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“…A syndrome of familial juvenile hyperuricemic nephropathy (FJHN [MIM 162000]) is an autosomal dominant disorder in which abnormal renal tubular excretion of uric acid and gout are associated with the late development of interstitial nephritis and progressive renal failure [44,45,46].…”

Section: Genetic Transmission Is Autosomal Dominantmentioning

confidence: 99%

“…An interesting new mechanism for hyperuricemia has been recently discovered in FJHN [45,46]. It is to pathologic findings in FJHN raised similarities with autosomal dominant medullary cystic kidney disease (MCKD [MIM 174000]).…”

Section: Biochemical and Molecular Featuresmentioning

confidence: 99%