Molecular Basis of Familial Hyperuricemic Nephropathies
Molekulární podstata familiárních hyperurikemických nefropatií
dissertation thesis (DEFENDED)
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http://hdl.handle.net/20.500.11956/25566Identifiers
Study Information System: 83596
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- Kvalifikační práce [4468]
Author
Advisor
Referee
Jirsa, Milan
Sedláček, Zdeněk
Faculty / Institute
First Faculty of Medicine
Discipline
-
Department
Institute of Inherited Metabolic Disorders First Faculty of Medicine Charles University in Prague
Date of defense
11. 3. 2010
Publisher
Univerzita Karlova, 1. lékařská fakultaLanguage
English
Grade
Pass
In 1960 Duncan and Dixon described family whth chronic tubulointerstitial kidney disease associated with juvenile onset of hyperuricemia and gout. Based on combination of these clinical symptoms they named the disease familial juvenile hyperuricemic nephropathy (FJHN) [1]. Disease with very similar clinical presentation but different age of onset and kidney histology was described as a medullary cystic kidney disease (MCKD) in 1977 [2]. Until recently the molecular basis and pathogenesis of this syndrome remained unknown. The long term aim of our research group is to elucidate the genetic basis of the disease and to solve pathogenetic mechanisms leading to the individual clinical and biochemical symptoms (e.g. hyperuricemia) and kidney damage in general. We systematically identify patients with this disease and healthy family members and collect relevant clinical information and samples for classification (urine, blood, tissue biopsies) and subsequent clinical, biochemical, molecular biology and cell pathology correlations. We [3, 4] and others [5-7] proved genetic heterogeneity of FJHN and defined four FJHN loci on chromosomes 1q21, 1q41, 16p11.2. and 17q21.3. Further research defined disease causing mutations in three genes - uromodulin (UMOD) [8], hepatonuclear factor 1-beta (HNF-1) [9] and renin (REN)...