https://novaprd-lb.newcastle.edu.au/vital/access/manager/Index ${session.getAttribute("locale")} 5 Carbimazole/methimazole embryopathy in siblings: a possible genetic susceptibility https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:23675 Wed 11 Apr 2018 09:48:05 AEST ]]> Knowledge of risk management strategies, and information and risk management preferences of women at increased risk for ovarian cancer https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:526 Thu 25 Jul 2013 09:10:32 AEST ]]> Atypical Angelman syndrome with macrocephaly due to a familial imprinting center deletion https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:5230 Sat 24 Mar 2018 07:44:18 AEDT ]]> Recognizable cerebellar dysplasia associated with mutations in multiple tubulin genes https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:26556 Sat 24 Mar 2018 07:26:14 AEDT ]]> Diverse phenotypic consequences of mutations affecting the C-terminus of FLNA https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:22694 FLNA, cross-links cytoskeletal actin into three-dimensional networks, facilitating its role as a signalling scaffold and a mechanosensor of extrinsic shear forces. Central to these functions is the ability of FLNA to form V-shaped homodimers through its C-terminal located filamin repeat 24. Additionally, many proteins that interact with FLNA have a binding site that includes the C-terminus of the protein. Here, a cohort of patients with mutations affecting this region of the protein is studied, with particular emphasis on the phenotype of male hemizygotes. Seven unrelated families are reported, with five exhibiting a typical female presentation of periventricular heterotopia (PH), a neuronal migration disorder typically caused by loss-of-function mutations in FLNA. One male presents with widespread PH consistent with previous male phenotypes attributable to hypomorphic mutations in FLNA. In stark contrast, two brothers are described with a mild PH presentation, due to a missense mutation (p.Gly2593Glu) inserting a large negatively charged amino acid into the hydrophobic dimerisation interface of FLNA. Co-immunoprecipitation, in vitro cross-linking studies and gel filtration chromatography all demonstrated that homodimerisation of isolated FLNA repeat 24 is abolished by this p.Gly2593Glu substitution but that extended FLNAGly2593Glu repeat 16–24 constructs exhibit dimerisation. These observations imply that other interactions apart from those mediated by the canonical repeat 24 dimerisation interface contribute to FLNA homodimerisation and that mutations affecting this region of the protein can have broad phenotypic effects.]]> Sat 24 Mar 2018 07:11:12 AEDT ]]>