| 1. |
|
|
| 2. |
- Schwantje, M., et al.
(författare)
-
Thermo-sensitive mitochondrial trifunctional protein deficiency presenting with episodic myopathy
- 2022
-
Ingår i: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 45:4, s. 819-831
-
Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial trifunctional protein (MTP) is involved in long-chain fatty acid beta-oxidation (lcFAO). Deficiency of one or more of the enzyme activities as catalyzed by MTP causes generalized MTP deficiency (MTPD), long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), or long-chain ketoacyl-CoA thiolase deficiency (LCKATD). When genetic variants result in thermo-sensitive enzymes, increased body temperature (e.g. fever) can reduce enzyme activity and be a risk factor for clinical decompensation. This is the first description of five patients with a thermo-sensitive MTP deficiency. Clinical and genetic information was obtained from clinical files. Measurement of LCHAD and LCKAT activities, lcFAO-flux studies and palmitate loading tests were performed in skin fibroblasts cultured at 37 degrees C and 40 degrees C. In all patients (four MTPD, one LCKATD), disease manifested during childhood (manifestation age: 2-10 years) with myopathic symptoms triggered by fever or exercise. In four patients, signs of retinopathy or neuropathy were present. Plasma long-chain acylcarnitines were normal or slightly increased. HADHB variants were identified (at age: 6-18 years) by whole exome sequencing or gene panel analyses. At 37 degrees C, LCHAD and LCKAT activities were mildly impaired and lcFAO-fluxes were normal. Remarkably, enzyme activities and lcFAO-fluxes were markedly diminished at 40 degrees C. Preventive (dietary) measures improved symptoms for most. In conclusion, all patients with thermo-sensitive MTP deficiency had a long diagnostic trajectory and both genetic and enzymatic testing were required for diagnosis. The frequent absence of characteristic acylcarnitine abnormalities poses a risk for a diagnostic delay. Given the positive treatment effects, upfront genetic screening may be beneficial to enhance early recognition.
|
|
| 3. |
- Le Coroller, H., et al.
(författare)
-
The Carlina-type diluted telescope Stellar fringes on Deneb
- 2015
-
Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 573
-
Tidskriftsartikel (refereegranskat)abstract
- Context. The performance of interferometers has been much increased over the past ten years. But the number of observable objects is still limited by the low sensitivity and imaging capability of the current facilities. Studies have been conducted with the aim to propose a new generation of interferometers. Aims. The Carlina concept studied at the Haute-Provence Observatory consists of an optical interferometer configured as a diluted version of the Arecibo radio telescope: above the diluted primary mirror made of fixed co-spherical segments, a helium balloon or cables that are suspended between two mountains and/or pylons carry a gondola containing the focal optics. This concept does not require delay lines. Methods. Since 2003, we have been building a technical demonstrator of this diluted telescope. The main goals of this project were to find opto-mechanical solutions to stabilize the optics attached to cables at several tens of meters above the ground, and to characterize this diluted telescope under real conditions. In 2012, we obtained metrology fringes, and co-spherized the primary mirrors within one micron accuracy. In 2013, we tested the whole optical train: servo loop, metrology, and the focal gondola. Results. We obtained stellar fringes on Deneb in September 2013. We here present the characteristics of these observations: quality of the guiding, signal-to-noise ratio reached, and possible improvements for a future system. Conclusions. By detecting fringes on Deneb, we confirm that the entire system conceptually has worked correctly. It also proves that when the primary mirrors are aligned using the metrology system, we can directly record fringes in the focal gondola, even in blind operation. It is an important step that demonstrates the feasibility of building a diluted telescope using cables strained between cliffs or pylons. Carlina, like the Multiple Mirror Telescope (MMT) or Large Binocular Telescope (LBT), could be one of the first members of a new class of telescopes named large diluted telescopes. Its optical architecture has many advantages for future projects: Planet Formation Imager (PFI), post-ELTs, interferometer in space.
|
|
| 4. |
- Ng, Bobby G, et al.
(författare)
-
ALG1-CDG: Clinical and Molecular Characterization of 39 Unreported Patients.
- 2016
-
Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794.
-
Tidskriftsartikel (refereegranskat)abstract
- Congenital disorders of glycosylation (CDG) arise from pathogenic mutations in over one hundred genes leading to impaired protein or lipid glycosylation. ALG1 encodes a β1,4 mannosyltransferase that catalyzes the addition of the first of nine mannose moieties to form a dolichol-lipid linked oligosaccharide intermediate (DLO) required for proper N-linked glycosylation. ALG1 mutations cause a rare autosomal recessive disorder termed ALG1-CDG. To date thirteen mutations in eighteen patients from fourteen families have been described with varying degrees of clinical severity. We identified and characterized thirty-nine previously unreported cases of ALG1-CDG from thirty-two families and add twenty-six new mutations. Pathogenicity of each mutation was confirmed based on its inability to rescue impaired growth or hypoglycosylation of a standard biomarker in an alg1-deficient yeast strain. Using this approach we could not establish a rank order comparison of biomarker glycosylation and patient phenotype, but we identified mutations with a lethal outcome in the first two years of life. The recently identified protein-linked xeno-tetrasaccharide biomarker, NeuAc-Gal-GlcNAc2 , was seen in all twenty-seven patients tested. Our study triples the number of known patients and expands the molecular and clinical correlates of this disorder. This article is protected by copyright. All rights reserved.
|
|
