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Le Touquet – Paris-Plage, France

Groome J.R.,Idaho State University | Jurkat-Rott K.,University of Ulm | Jurkat-Rott K.,Rare Disease Center | Lehmann-Horn F.,University of Ulm | Lehmann-Horn F.,Rare Disease Center
Channels | Year: 2014

Heterologous expression of sodium channel mutations in hypokalemic periodic paralysis reveals 2 variants on channel dysfunction. Charge-reducing mutations of voltage sensing S4 arginine residues alter channel gating as typically studied with expression in mammalian cells. These mutations also produce leak currents through the voltage sensor module, as typically studied with expression in Xenopus oocytes. DIIIS4 mutations at R3 in the skeletal muscle sodium channel produce gating defects and omega current consistent with the phenotype of reduced excitability. Here, we confirm DIIIS4 R3C gating defects in the oocyte expression system for fast inactivation and its recovery. We provide novel data for the effects of the cysteine mutation on voltage sensor movement, to further our understanding of sodium channel defects in hypokalemic periodic paralysis. Gating charge movement and its remobilization are selectively altered by the mutation at hyperpolarized membrane potential, as expected with reduced serum potassium. © James R Groome, Karin Jurkat-Rott, and Frank Lehmann-Horn.

Weber J.J.,University of Tubingen | Weber J.J.,Rare Disease Center | Sowa A.S.,University of Tubingen | Sowa A.S.,Rare Disease Center | And 4 more authors.
BioMed Research International | Year: 2014

The history of polyglutamine diseases dates back approximately 20 years to the discovery of a polyglutamine repeat in the androgen receptor of SBMA followed by the identification of similar expansion mutations in Huntington's disease, SCA1, DRPLA, and the other spinocerebellar ataxias. This common molecular feature of polyglutamine diseases suggests shared mechanisms in disease pathology and neurodegeneration of disease specific brain regions. In this review, we discuss the main pathogenic pathways including proteolytic processing, nuclear shuttling and aggregation, mitochondrial dysfunction, and clearance of misfolded polyglutamine proteins and point out possible targets for treatment. © 2014 Jonasz Jeremiasz Weber et al.

Beauquier-Maccotta B.,University of Paris Descartes | Chalouhi G.E.,University of Paris Descartes | Chalouhi G.E.,Rare Disease Center | Picquet A.-L.,Rare Disease Center | And 6 more authors.
PLoS ONE | Year: 2016

Monochronioric (MC) twin pregnancies are considered as high-risk pregnancies with potential complications requiring in-utero interventions. We aimed to assess prenatal attachment, anxiety, post-traumatic stress disorder (PTSD) and depressive symptoms in MC pregnancies complicated with Twin-To-Twin-transfusion syndrome (TTTS) in comparison to uncomplicated monochorionic (UMC) and dichorionic pregnancies (DC). Auto-questionnaires were filled out at diagnosis of TTTS and at successive milestones. Prenatal attachment, PTSD, anxiety and perinatal depression were evaluated respectively by the Prenatal Attachment Inventory (PAI) completed for each twin, the Post-traumatic Checklist Scale (PCLS), the State-Trait Anxiety Inventory (STAI) and the Edinburgh Perinatal Depression Scale (EPDS). There was no significant difference in the PAI scores between the two twins. In the DC and UMC groups, PAI scores increased throughout pregnancy, whilst it didn't for TTTS group. TTTS and DC had a similar prenatal attachment while MC mothers expressed a significantly higher attachment to their fetuses and expressed it earlier. At the announcement of TTTS, 72%of the patients present a score over the threshold at the EPDS Scale, with a higher score for TTTS than for DC (p = 0.005), and UMC (p = 0.007) at the same GA. 30%of mothers in TTTS group have PTSD during pregnancy. 50%of TTTS-patients present an anxiety score over the threshold (STAIScale), with a score significantly higher in TTTS than in UMC (p<0.001) or DC (p<0.001). The proportion of subject with a STAI-State over the threshold is also significantly higher in TTTS than in DC at 20 GW(p = 0.01) and at 26 GW(p<0.05). The STAI-state scores in UMC and DC increase progressively during pregnancy while they decrease significantly in TTTS. TTTS announcement constitutes a traumatic event during a pregnancy with an important risk of PTSD, high level of anxiety and an alteration of the prenatal attachment. These results should guide the psychological support provided to these patients. Copyright © 2016 Beauquier-Maccotta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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