دورية أكاديمية
A cluster of mutations in the UMOD gene causes familial juvenile hyperuricemic nephropathy with abnormal expression of uromodulin.
| العنوان: | A cluster of mutations in the UMOD gene causes familial juvenile hyperuricemic nephropathy with abnormal expression of uromodulin. |
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| المؤلفون: | Dahan, Karin, Devuyst, Olivier, Smaers, Michèle, Vertommen, Didier, Loute, Guy, Poux, Jean-Michel, Viron, Béatrice, Jacquot, Christian, Gagnadoux, Marie-France, Chauveau, Dominique, Büchler, Mathias, Cochat, Pierre, Cosyns, Jean-Pierre, Mougenot, Béatrice, Rider, Mark, Antignac, Corinne, Dumoulin, Christine, Pirson, Yves |
| المساهمون: | UCL - MD/MINT - Département de médecine interne, UCL - MD/BICL - Département de biochimie et de biologie cellulaire, UCL - MD/MNOP - Département de morphologie normale et pathologique, UCL - (SLuc) Service de néphrologie, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Centre de pathologie anorectale de l'enfant |
| المصدر: | Journal of the American Society of Nephrology, Vol. 14, no. 11, p. 2883-2893 (2003) |
| بيانات النشر: | American Society of Nephrology |
| سنة النشر: | 2003 |
| المجموعة: | DIAL@UCL (Université catholique de Louvain) |
| مصطلحات موضوعية: | Adolescent, Adult, Child, Preschool, DNA Mutational Analysis, Exons, Female, Humans, Hyperuricemia, Kidney Failure, Chronic, Loop of Henle, Male, Middle Aged, Mucoproteins, Multigene Family, Mutation, Pedigree |
| الوصف: | Familial juvenile hyperuricemic nephropathy (FJHN [MIM 162000]) is an autosomal-dominant disorder characterized by abnormal tubular handling of urate and late development of chronic interstitial nephritis leading to progressive renal failure. A locus for FJHN was previously identified on chromosome 16p12 close to the MCKD2 locus, which is responsible for a variety of autosomal-dominant medullary cystic kidney disease (MCKD2). UMOD, the gene encoding the Tamm-Horsfall/uromodulin protein, maps within the FJHN/MCKD2 critical region. Mutations in UMOD were recently reported in nine families with FJHN/MCKD2 disease. A mutation in UMOD has been identified in 11 FJHN families (10 missense and one in-frame deletion)-10 of which are novel-clustering in the highly conserved exon 4. The consequences of UMOD mutations on uromodulin expression were investigated in urine samples and renal biopsies from nine patients in four families. There was a markedly increased expression of uromodulin in a cluster of tubule profiles, suggesting an accumulation of the protein in tubular cells. Consistent with this observation, urinary excretion of wild-type uromodulin was significantly decreased. The latter findings were not observed in patients with FJHN without UMOD mutations. In conclusion, this study points to a mutation clustering in exon 4 of UMOD as a major genetic defect in FJHN. Mutations in UMOD may critically affect the function of uromodulin, resulting in abnormal accumulation within tubular cells and reduced urinary excretion. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1046-6673 1533-3450 |
| العلاقة: | boreal:9647; http://hdl.handle.net/2078.1/9647Test; info:pmid/14569098; urn:ISSN:1046-6673; urn:EISSN:1533-3450 |
| DOI: | 10.1097/01.ASN.0000092147.83480.B5 |
| الإتاحة: | https://doi.org/10.1097/01.ASN.0000092147.83480.B5Test http://hdl.handle.net/2078.1/9647Test |
| حقوق: | info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.1AE31590 |
| قاعدة البيانات: | BASE |
| تدمد: | 10466673 15333450 |
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| DOI: | 10.1097/01.ASN.0000092147.83480.B5 |