Heterozygous cis HYDIN mutations cause primary ciliary dyskinesia.

Background: The product of ciliary gene HYDIN is an integral component for c2b projection within the motile cilia central pair (CP) apparatus. Biallelic mutations of this gene cause primary ciliary dyskinesia (PCD), an uncommon heterogeneous recessive disorder affecting motile cilia, resulting in defective mucociliary clearance that leads to chronic suppurative lung disease.

Methods: Nasal brushing samples were collected from two siblings attending the Victorian Diagnostic service for PCD.

Altered airway ciliary orientation in patients with X-linked retinitis pigmentosa.

Previous reports suggested links between respiratory ciliary dysfunction and primary ciliopathies such as X-linked retinitis pigmentosa (XLRP). To investigate if patients with XLRP have abnormal airway ciliary structure or function, we assessed respiratory ciliary beat pattern and ultrastructure, including ciliary orientation, in 12 patients with XLRP without respiratory disease and 10 control subjects. Patients with XLRP had normal ciliary ultrastructure but significantly (p=0.

Identification of an Immortalized Human Airway Epithelial Cell Line with Dyskinetic Cilia.

Primary ciliary dyskinesia is an inherited, currently incurable condition. In the respiratory system, primary ciliary dyskinesia causes impaired functioning of the mucociliary escalator, leading to nasal congestion, cough, and recurrent otitis media, and commonly progresses to cause more serious and permanent damage, including hearing deficits, chronic sinusitis, and bronchiectasis. New treatment options for the condition are thus necessary.

Abnormal Processing of Autophagosomes in Transformed B Lymphocytes from SCARB2-Deficient Subjects.

Mutations of the intrinsic lysosomal membrane protein SCARB2 cause action myoclonus-renal failure syndrome (AMRF syndrome), a rare disease characterized by renal and neurological manifestations. In this study, examination of Cos7 cells transfected with SCARB2 cDNA derived from two patients with AMRF syndrome showed that the resultant protein was truncated and was not incorporated into vesicular structures, as occurred with full-length SCARB2 cDNA. Mutant SCARB2 protein failed to colocalize with lysosomes and was found in the endoplasmic reticulum or the cytosol indicating a loss of function.

Activation of Src induces mitochondrial localisation of de2-7EGFR (EGFRvIII) in glioma cells: implications for glucose metabolism.

A common mutation of the epidermal growth factor receptor in glioma is the de2-7EGFR (or EGFRvIII). Glioma cells expressing de2-7EGFR contain an intracellular pool of receptor with high levels of mannose glycosylation, which is consistent with delayed processing. We now show that this delay occurs in the Golgi complex.

The risks of thin basement membrane nephropathy.

Most individuals with thin basement membrane nephropathy (TBMN) have an excellent prognosis. For these patients, the only hazards are the anxiety related to misconceptions about the diagnosis and the inconvenience, expense, and wastefulness of unnecessary investigations. However, there also are specific genetic implications for individuals with TBMN because, on average, half their offspring inherit the causative mutations and most of these have hematuria.

A synthetic heparanase inhibitor reduces proteinuria in passive Heymann nephritis.

The beta-D-endoglycosidase heparanase has been proposed to be important in the pathogenesis of proteinuria by acting to selectively degrade the negatively charged side chains of heparan sulfate proteoglycans (HSPG) within the glomerular basement membrane (GBM). A loss of the negatively charged HSPG may result in alteration of the permselective properties of the GBM, loss of glomerular epithelial and endothelial cell anchor points, and liberation of growth factors. This study examined the effect of PI-88, a sulfated oligosaccharide heparanase inhibitor, on renal function, glomerular ultrastructure, and proteinuria.