| 1. |
|
|
| 2. |
- Nilsson, Jakob, et al.
(författare)
-
3-Alkyl- and 3-amido-isothiazoloquinolin-4-ones as ligands for the benzodiazepine site of GABA(A) receptors.
- 2011
-
Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X.
-
Tidskriftsartikel (refereegranskat)abstract
- Based on a pharmacophore model of the benzodiazepine binding site of the GABA(A) receptors, developed with synthetic flavones and potent 3-carbonylquinolin-4-ones, 3-alkyl- and 3-amido-6-methylisothiazoloquinolin-4-ones were designed, prepared and assayed. The suggestion that the interaction between the hydrogen bond donor site H1 with the 3-carbonyl oxygen in 3-carbonylquinolin-4-ones can be replaced by an interaction between H1 and N-2 in the isothiazoloquinolin-4-ones, was confirmed. As with the 3-carbonylquinolin-4-ones, the length of the chain in position 3 is critical for an efficient interaction with the lipophilic pockets of the pharmacophore model. The most potent 3-alkyl derivative, 3-pentyl-6-methylisothiazoloquinolin-4-one, has an affinity (K(i) value) for the benzodiazepine binding site of the GABA(A) receptors of 13nM. However, by replacing the 3-pentyl with a 3-butyramido group an even more potent compound was obtained, with a K(i) value of 2.8nM, indicating that the amide function facilitates additional interactions with the binding site.
|
|
| 3. |
- Ostergaard, Elsebet, et al.
(författare)
-
A novel missense mutation in SUCLG1 associated with mitochondrial DNA depletion, encephalomyopathic form, with methylmalonic aciduria.
- 2010
-
Ingår i: European journal of pediatrics. - : Springer Science and Business Media LLC. - 1432-1076 .- 0340-6199. ; 169:2, s. 201-5
-
Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial DNA depletion, encephalomyopathic form, with methylmalonic aciduria is associated with mutations in SUCLA2, the gene encoding a beta subunit of succinate-CoA ligase, where 17 patients have been reported. Mutations in SUCLG1, encoding the alpha subunit of the enzyme, have been reported in only one family, where a homozygous 2 bp deletion was associated with fatal infantile lactic acidosis. We here report a patient with a novel homozygous missense mutation in SUCLG1, whose phenotype is similar to that of patients with SUCLA2 mutations.
|
|
| 4. |
- Sofou, Kalliopi, et al.
(författare)
-
A multicenter study on Leigh syndrome: disease course and predictors of survival.
- 2014
-
Ingår i: Orphanet journal of rare diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite the fact that Leigh syndrome is the most common phenotype of mitochondrial disorders in children, longitudinal natural history data is missing. This study was undertaken to assess the phenotypic and genotypic spectrum of patients with Leigh syndrome, characterise the clinical course and identify predictors of survival in a large cohort of patients.
|
|
| 5. |
- Sofou, Kalliopi, et al.
(författare)
-
Phenotype-genotype correlations in Leigh syndrome: new insights from a multicentre study of 96 patients.
- 2018
-
Ingår i: Journal of medical genetics. - : BMJ. - 1468-6244 .- 0022-2593. ; 55:1, s. 21-27
-
Tidskriftsartikel (refereegranskat)abstract
- Leigh syndrome is a phenotypically and genetically heterogeneous mitochondrial disorder. While some genetic defects are associated with well-described phenotypes, phenotype-genotype correlations in Leigh syndrome are not fully explored.We aimed to identify phenotype-genotype correlations in Leigh syndrome in a large cohort of systematically evaluated patients.We studied 96 patients with genetically confirmed Leigh syndrome diagnosed and followed in eight European centres specialising in mitochondrial diseases.We found that ataxia, ophthalmoplegia and cardiomyopathy were more prevalent among patients with mitochondrial DNA defects. Patients with mutations in MT-ND and NDUF genes with complex I deficiency shared common phenotypic features, such as early development of central nervous system disease, followed by high occurrence of cardiac and ocular manifestations. The cerebral cortex was affected in patients with NDUF mutations significantly more often than the rest of the cohort. Patients with the m.8993T>Gmutation in MT-ATP6 gene had more severe clinical and radiological manifestations and poorer disease outcome compared with patients with the m.8993T>Cmutation.Our study provides new insights into phenotype-genotype correlations in Leigh syndrome and particularly in patients with complex I deficiency and with defects in the mitochondrial ATP synthase.
|
|
