tamatokyo.blogg.se - The long dark umod

familial juvenile hyperuricaemic nephropathy.

We postulate that mutation of UMOD disrupts the tertiary structure of UMOD and is responsible for the clinical changes of interstitial renal disease, polyuria, and hyperuricaemia found in MCKD2 and FJHN. UMOD is a GPI anchored glycoprotein and the most abundant protein in normal urine. Results: We identified four novel uromodulin ( UMOD) gene mutations that segregate with the disease phenotype in three families with FJHN and in one family with MCKD2.Ĭonclusion: These data provide the first direct evidence that MCKD2 and FJHN arise from mutation of the UMOD gene and are allelic disorders. DNA sequencing of candidate genes was performed to detect mutations in subjects affected with FJHN (three unrelated families) and MCKD2 (one family). To permit refinement of the candidate interval and localisation of candidate genes, an integrated physical and genetic map of the candidate region was developed. Methods: Two large, multigenerational families segregating FJHN were studied by genetic linkage and haplotype analyses to sublocalise the chromosome 16p FJHN gene locus. These clinical and genetic findings suggest that these conditions may be allelic.Īim: To identify the gene and associated mutation(s) responsible for FJHN and MCKD2.

Genetic linkage studies have localised genes for both conditions to overlapping regions of chromosome 16p11-p13. Often definitive diagnosis is possible only after significant pathology has occurred. Clinical features of both conditions vary in presence and severity. Introduction: Medullary cystic kidney disease 2 (MCKD2) and familial juvenile hyperuricaemic nephropathy (FJHN) are both autosomal dominant renal diseases characterised by juvenile onset of hyperuricaemia, gout, and progressive renal failure. Correspondence to: Dr T C Hart, Center for Craniofacial and Dental Genetics, University of Pittsburgh, School of Dental Medicine, 614 Salk Hall, Terrace Street, Pittsburgh, PA 15261, USA.8Section on Nephrology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157, USA.7Beijing Medical University, Beijing, China.6University of Pittsburgh, School of Medicine, Pittsburgh, PA 15261, USA.5Department of Urology, Cornell Medical School, New York, NY 10021, USA.4Department of Pathology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157, USA.3Bakersville Community Medical Clinic Inc, 86 N Mitchell Avenue, Bakersville, NC 28705, USA.2Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.1University of Pittsburgh, School of Dental Medicine, Division of Oral Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.