L P Van Den Heuvel | PubMed Health

PubMed2001

Respiratory chain complex I deficiency.

Oxidative phosphorylation disorders make a contribution of 1 per 10,000 live births in man, of which isolated complex I deficiency is frequently the cause. Complex I, or NADH:ubiquinone oxidoreductase, is the largest multi-protein enzyme complex of the mitochondrial electron transfer chain. In complex I deficiency, various clinical phenotypes have been recognized, often resulting in multi-system disorders with a fatal outcome at a young age. Recent advances in complex I deficiency, regarding clinical, biochemical, and molecular aspects are described. However, the genetic causes of about 60% of complex I deficiency remain unclear. As a consequence, further research will be needed to clarify the genetic defects in the remaining cases. Novel strategies in which interesting non-structural nuclear-encoded disease-causing genes may be found, as well as the molecular genetic composition of human complex I, are presented.

Cell Nucleus↗

PubMed2000

Four novel mutations in the tyrosine hydroxylase gene in patients with infantile parkinsonism.

Mutation detection in the tyrosine hydroxylase gene (TH) was performed in patients from two families. DNA sequencing revealed the presence of four novel missense mutations (exon 9 and 14 in family A, exon 8 and 9 in family B); the mutations were confirmed with restriction enzyme analysis, and did not occur in control alleles. Three mutations are in the catalytic domain of the enzyme and one may disturb tetramerization. At the moment, all patients are in the fourth decade of life. For more than 30 years they have been able to live a normal life with low-dose L-DOPA medication.

Adult↗

PubMed1998

Effect of plasma from patients with idiopathic nephrotic syndrome on proteoglycan synthesis by human and rat glomerular cells.

In vivo and in vitro findings have shown that plasma of patients with idiopathic nephrotic syndrome (INS) contain factors that increase glomerular permeability to proteins. The effects of these factors on proteoglycan synthesis by glomerular cells are unknown. To investigate the effect of plasma from patients with INS (n = 23) and other glomerulopathies (n = 12) on the amount of proteoglycans synthesized by cultured rat mesangial cells and human glomerular epithelial cells, glomerular cells were cultured for 24 h with plasma from patients or control subjects, and incorporation of Na2(35)SO4 in chondroitin dermatan sulfate and heparan sulfate was assessed using a cationic nylon membrane. The mean ratio of glycosaminoglycan produced by rat mesangial cells when in contact with plasma (5%) from INS patients to the amount produced when in contact with control plasma was 0.70+/-0.06. The mean ratio of heparan sulfate was 0.58+/-0.08. The decrease of heparan sulfate production was present in the cellular and in the extracellular fraction. It was observed when the cells were in contact with plasma from patients in relapse but not when in remission. No decrease of heparan sulfate production was observed with four of the five patients with membranous glomerulonephritis (ratio of 1.27+/-0.03), IgA nephropathy (n = 5, ratio of 1.27+/-0.03), and membranoproliferative glomerulonephritis (n = 2, ratio of 1.39+/-0.34). When human glomerular epithelial cells were exposed to 5% plasma from INS patients in relapse (n = 9), the mean ratio of heparan sulfate was 0.62+/-0.06 in the cellular fraction and 0.72+/-0.08 in the medium. When in contact with plasma from patients in remission, no difference of glycosaminoglycan production was observed. A factor present in plasma from patients with INS during initial episodes or relapses is able to decrease the proteoglycan production of glomerular cells.

Animals↗