Disorders of FZ-CRD; insights towards FZ-CRD folding and therapeutic landscape.

The ER is hub for protein folding. Proteins that harbor a Frizzled cysteine-rich domain (FZ-CRD) possess 10 conserved cysteine motifs held by a unique disulfide bridge pattern which attains a correct fold in the ER. Little is known about implications of disease-causing missense mutations within FZ-CRD families.

Electrical characterization of DNA supported on nitrocellulose membranes.

Integrated DNA-based nanoscale electronic devices will enable the continued realization of Moore's Law at the level of functional devices and systems. In this work, the electrical characterization of single and complementary base paired DNA has been directly measured and investigated via the use of nitrocellulose membranes. A radio frequency DAKS-3.

Improved plasma membrane expression of the trafficking defective P344R mutant of muscle, skeletal, receptor tyrosine kinase (MuSK) causing congenital myasthenic syndrome.

Muscle, skeletal, receptor tyrosine kinase (MuSK) is a key organizer at the postsynaptic membrane and critical for proper development and maintenance of the neuromuscular junction. Mutations in MUSK result in congenital myasthenic syndrome (CMS). We hypothesized that the CMS-causing missense mutation (P344R), found within the cysteine-rich domain of the protein, will affect its conformational tertiary structure.

Clinical and molecular analysis of a novel COLQ missense mutation causing congenital myasthenic syndrome in a Syrian family.

Background: Congenital myasthenic syndromes with end-plate acetylcholinesterase deficiency are rare autosomal recessive disorders characterized by onset of the disease in early childhood, general weakness exacerbated by exertion, ophthalmoplegia, and refractoriness to anticholinesterase drugs. To date, all reported cases have been attributed to mutations in 18 genes including the COLQ gene that encodes a specific collagen that anchors acetylcholinesterase at the basal lamina of the neuromuscular junction. We identified a Syrian family with two children of consanguineous parents from two branches affected with congenital myasthenic syndrome with end-plate acetylcholinesterase deficiency.

Identification of the cellular mechanisms that modulate trafficking of frizzled family receptor 4 (FZD4) missense mutants associated with familial exudative vitreoretinopathy.

Purpose: Fifteen missense mutations in the frizzled family receptor 4 (FZD4) reported to cause familial exudative vitreoretinopathy (FEVR) were evaluated to establish the pathological cellular mechanism of disease and to explore novel therapeutic strategies.

Methods: The mutations were generated by site-directed mutagenesis and expressed in HeLa and COS-7 cell lines. Confocal fluorescence microscopy and N-glycosylation profiling were used to observe the subcellular localization of the mutant proteins relative to wild-type (WT).

Novel KCNQ2 mutation in a large Emirati family with benign familial neonatal seizures.

Mutations in voltage-gated potassium channel Kv7.2 are responsible for benign familial neonatal seizures type 1, a rare monogenic autosomal dominant inherited epilepsy syndrome. We describe a novel mutation (c.

Endoplasmic reticulum quality control is involved in the mechanism of endoglin-mediated hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant genetic condition affecting the vascular system and is characterised by epistaxis, arteriovenous malformations and mucocutaneous and gastrointestinal telangiectases. This disorder affects approximately 1 in 8,000 people worldwide. Significant morbidity is associated with this condition in affected individuals, and anaemia can be a consequence of repeated haemorrhages from telangiectasia in the gut and nose.