Wolf, Matthias T. F. and Mucha, Bettina E. and Attanasio, Massimo and Zalewski, Isabella and Karle, Stephanie M. and Neumann, Hartmut P. H. and Rahman, Nazneen and Bader, Birgit and Baldamus, Conrad A. and Otto, Edgar and Witzgall, Ralph and Fuchshuber, Arno and Hildebrandt, Friedhelm (2003) Mutations of the Uromodulin gene in MCKD type 2 patients cluster in exon 4, which encodes three EGF-like domains. KIDNEY INTERNATIONAL, 64 (5). pp. 1580-1587. ISSN 0085-2538
Full text not available from this repository. (Request a copy)Abstract
Background. Autosomal-dominant medullary cystic kidney disease type 2 (MCKD2) is a tubulointerstitial nephropathy that causes renal salt wasting, hyperuricemia, gout, and end-stage renal failure in the fifth decade of life. The chromosomal locus for MCKD2 was localized on chromosome 16p12. Within this chromosomal region, Uromodulin (UMOD) was located as a candidate gene. UMOD encodes the Tamm-Horsfall protein. By sequence analysis, one group formerly excluded UMOD as the disease-causing gene. In contrast, recently, another group described mutations in the UMOD gene as responsible for MCKD2 and familial juvenile hyperuricemic nephropathy (FJHN). Methods. Haplotype analaysis for linkage to MCKD2 was performed in 25 MCKD families. In the kindreds showing linkage to the MCKD2 locus on chromosome 16p12, mutational analysis of the UMOD gene was performed by exon polymerase chain reaction (PCR) and direct sequencing. Results. In 19 families, haplotype analysis was compatible with linkage to the MCKD2 locus. All these kindreds were examined for mutations in the UMOD gene. In three different families, three novel heterozygous mutations in the UMOD gene were found and segregated with the phenotype in affected individuals. Mutations were found only in exon 4. Conclusion. We confirm the UMOD gene as the disease-causing gene for MCKD2. All three novel mutations were found in the fourth exon of UMOD, in which all mutations except one (this is located in the neighboring exon 5) published so far are located. These data point to a specific role of exon 4 encoded sequence of UMOD in the generation of the MCKD2 renal phenotype.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CYSTIC KIDNEY-DISEASE; JUVENILE HYPERURICEMIC NEPHROPATHY; TAMM-HORSFALL PROTEIN; HUMAN FIBRILLIN-1; LOCALIZATION; 16P12; NEPHRONOPHTHISIS; DYNAMICS; CHILDREN; BINDING; MCKD2; uromodulin; Tamm-Horsfall protein |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Molekulare und zelluläre Anatomie > Prof. Dr. Will Minuth |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Aug 2021 06:56 |
| Last Modified: | 30 Aug 2021 08:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/38477 |
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