Analysis of excretion fraction of uric acid.

Excretion fraction of uric acid (EFUA), is one of the most important hallmarks for diagnosis of familial juvenile hyperuricemic nephropathy (FJHN) and hereditary renal hypouricemia. EFUA was measured in 20 patients with FJHN. However, low excretion fraction (<6%) was found also in healthy FJHN family members and healthy controls (ref.

Mutations in TMEM76* cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome).

Mucopolysaccharidosis IIIC (MPS IIIC, or Sanfilippo C syndrome) is a lysosomal storage disorder caused by the inherited deficiency of the lysosomal membrane enzyme acetyl-coenzyme A: alpha -glucosaminide N-acetyltransferase (N-acetyltransferase), which leads to impaired degradation of heparan sulfate. We report the narrowing of the candidate region to a 2.6-cM interval between D8S1051 and D8S1831 and the identification of the transmembrane protein 76 gene (TMEM76), which encodes a 73-kDa protein with predicted multiple transmembrane domains and glycosylation sites, as the gene that causes MPS IIIC when it is mutated.

Antonín vancura and arterial hypertension. 50 years' evolution in the conception of pathogenesis and treatment of the disease.

A historical overview of the important contributions of Prof. Antonin Vancura from Charles University Medical Faculty, Prague, to the broader understanding of the pathogenesis, clinical course and classification of arterial hypertension is given in his pivotal publication and first Czech monography 'High Blood Pressure'. His unique clinical series of 1,096 hypertensive patients with their long-term follow-up after 5, 10 and 15 years made it possible to work out the classification of hypertension not only on the basis of blood pressure readings, but also according to target organ damage--a principle which is close to the 2003 classification of the European Society of Hypertension/European Society of Cardiology (ESH/ESC).

Alterations of uromodulin biology: a common denominator of the genetically heterogeneous FJHN/MCKD syndrome.

Autosomal dominant hyperuricemia, gout, renal cysts, and progressive renal insufficiency are hallmarks of a disease complex comprising familial juvenile hyperuricemic nephropathy and medullary cystic kidney diseases type 1 and type 2. In some families the disease is associated with mutations of the gene coding for uromodulin, but the link between the genetic heterogeneity and mechanism(s) leading to the common phenotype symptoms is not clear. In 19 families, we investigated relevant biochemical parameters, performed linkage analysis to known disease loci, sequenced uromodulin gene, expressed and characterized mutant uromodulin proteins, and performed immunohistochemical and electronoptical investigation in kidney tissues.

Mapping of a new candidate locus for uromodulin-associated kidney disease (UAKD) to chromosome 1q41.

Background: Autosomal-dominant juvenile hyperuricemia, gouty arthritis, medullary cysts, and progressive renal insufficiency are features associated with familial juvenile hyperuricemic nephropathy (FJHN), medullary cystic kidney disease type 1 (MCKD1) and type 2 (MCKD2). MCKD1 has been mapped to chromosome 1q21. FJHN and MCKD2 have been mapped to chromosome 16p11.

Familial juvenile hyperuricaemic nephropathy (FJHN): linkage analysis in 15 families, physical and transcriptional characterisation of the FJHN critical region on chromosome 16p11.2 and the analysis of seven candidate genes.

Familial juvenile hyperuricaemic nephropathy (FJHN) is an autosomal dominant renal disease characterised by juvenile onset of hyperuricaemia, gouty arthritis, and progressive renal failure at an early age. Recent studies in four kindreds showed linkage of a gene for FJHN to the same genomic interval on chromosome 16p11.2, where the gene for the phenotypically similar medullary cystic disease type 2 (MCKD2) has been localised.

Human adenylosuccinate lyase (ADSL), cloning and characterization of full-length cDNA and its isoform, gene structure and molecular basis for ADSL deficiency in six patients.

Adenylosuccinate lyase (ADSL) is a bifunctional enzyme acting in de novo purine synthesis and purine nucleotide recycling. ADSL deficiency is a selectively neuronopathic disorder with psychomotor retardation and epilepsy as leading traits. Both dephosphorylated enzyme substrates, succinylaminoimidazole-carboxamide riboside (SAICAr) and succinyladenosine (S-Ado), accumulate in the cerebrospinal fluid (CSF) of affected individuals with S-Ado/SAICAr concentration ratios proportional to the phenotype severity.

Metabolic, humoral and haemodynamic characteristics of normotensive offspring from hypertensive families.

Arterial hypertension is not only a haemodynamic abnormality, but it is associated with several metabolic and humoral changes. Heredity appears to be participating in the pathogenesis of essential hypertension (EH). We studied whether some metabolic, humoral and haemodynamic changes could be detected in genetically predisposed normotensive sons of hypertensive families (SH) compared with normotensive sons of normotensive parents (SN).

Heart in thyroid diseases.

The paper examines the basic pathophysiologic mechanisms playing a role in the development of cardiovascular changes on thyroid hyper- and hypofunction. The haemodynamic changes typically associated with increased and decreased secretion of thyroid hormones are described and compared. Using echocardiography, the haemodynamics changes are documented in 12 patients with hyperthyroidism and 19 patients with myxoedema prior to thyrostatic and substitution therapy.