Search results for "amino acid substitution"

Non-classic cystic fibrosis associated with D1152HCFTR mutation

2010

Burgel P-R, Fajac I, Hubert D, Grenet D, Stremler N, Roussey M, Siret D, Languepin J, Mely L, Fanton A, Labbe A, Domblides P, Vic P, Dagorne M, Reynaud-Gaubert M, Counil F, Varaigne F, Bienvenu T, Bellis G, Dusser D. Non-classic cystic fibrosis associated with D1152H CFTR mutation. Background: Limited knowledge exists on phenotypes associated with the D1152H cystic fibrosis transmembrane conductance regulator (CFTR) mutation. Methods: Subjects with a D1152H allele in trans with another CFTR mutation were identified using the French Cystic Fibrosis Registry. Phenotypic characteristics were compared with those of pancreatic insufficient (PI) and pancreatic sufficient (PS) cystic fibrosis (CF)…

Mutations in the skeletal muscle alpha-actin gene in patients with actin myopathy and nemaline myopathy

1999

Muscle contraction results from the force generated between the thin filament protein actin and the thick filament protein myosin, which causes the thick and thin muscle filaments to slide past each other. There are skeletal muscle, cardiac muscle, smooth muscle and non-muscle isoforms of both actin and myosin. Inherited diseases in humans have been associated with defects in cardiac actin (dilated cardiomyopathy and hypertrophic cardiomyopathy), cardiac myosin (hypertrophic cardiomyopathy) and non-muscle myosin (deafness). Here we report that mutations in the human skeletal muscle alpha-actin gene (ACTA1) are associated with two different muscle diseases, 'congenital myopathy with excess o…

Superficial thrombophlebitis in varicose vein disease: the particular role of methylenetetrahydrofolate reductase.

2010

Background The purpose of this study was to compare the genetic background of superficial (SVT) and deep vein thrombosis (DVT). Methods Factor V (FV)-Leiden (G16891A)-, factor II(G20210A)-mutations, protein C- and S, as well as methylenetetrahydrofolate reductase (MTHFR) polymorphisms at C677T and A1298C, and serum homocysteine levels (hcy) were determined in 29 patients with SVT and 26 with DVT. Findings FV- and –II-mutations were less frequent in patients with SVT (2/3) compared with DVT (9/5), respectively ( P < 0.002 in case of FV). However, the frequency of the MTHFR C677T polymorphism was significantly higher in patients with SVT compared with DVT (CT 12 versus 10, and TT 7 versus …

Sex differences in allelic frequencies of the 5-HT2C Cys23Ser polymorphism in psychiatric patients and healthy volunteers: findings from an associati…

2000

Polymorphisms in the serotonergic system are believed to play a role in the etiology and treatment of different psychiatric illnesses. The 5-HT2C receptor gene is X-linked, with a frequent mutation at nucleotide 68 leading to a Ser-->Cys transition at amino acid 23. Recent studies have demonstrated an impaired function of 5-HT2C receptors and an increased production of the major noradrenergic metabolite 3-methoxy-4-hydroxyphenylethyleneglycol in the cerebrospinal fluid among the subjects carrying the Ser23 allele (Lappalainen et al., 1999). Biol. Psychiatry 46:821). We genotyped patients with alcohol dependence, panic disorder without agoraphobia, generalized anxiety disorder, narcolepsy an…

Association study of a SNP coding for a M129V substitution in the prion protein in schizophrenia.

2003

Assessment of determinants affecting the dual topology of hepadnaviral large envelope proteins

2004

For functional diversity, the large (L) envelope protein of hepatitis B virus (HBV) acquires a dual transmembrane topology via co-translational membrane integration of the S region and partial post-translational translocation of the preS subdomain. Because each process requires the second transmembrane segment (TM2), we explored the action of this determinant by using protease protection analysis of mutant L proteins. We demonstrated that neither the disruption of a leucine zipper-like motif by multiple alanine substitutions nor the flanking charges of TM2 affected the topological reorientation of L. The dispensability of both putative subunit interaction modules argues against a link betwe…

The Fumarate/Succinate Antiporter DcuB of Escherichia coli Is a Bifunctional Protein with Sites for Regulation of DcuS-dependent Gene Expression

2008

DcuB of Escherichia coli catalyzes C4-dicarboxylate/succinate antiport during growth by fumarate respiration. The expression of genes of fumarate respiration, including the genes for DcuB (dcuB) and fumarate reductase (frdABCD) is transcriptionally activated by C4-dicarboxylates via the DcuS-DcuR two-component system, comprising the sensor kinase DcuS, which contains a periplasmic sensing domain for C4-dicarboxylates. Deletion or inactivation of dcuB caused constitutive expression of DcuS-regulated genes in the absence of C4-dicarboxylates. The effect was specific for DcuB and not observed after inactivation of the homologous DcuA or the more distantly related DcuC transporter. Random and s…

Relevant associations of the glucokinase regulatory protein/glucokinase gene variation with TAG concentrations in a high-cardiovascular risk populati…

2012

The SNP rs1260326 (P446L) and rs1799884 ( − 30G>A) for the glucokinase regulatory protein (GCKR) and glucokinase (GCK) genes, respectively, have been associated with opposing effects on TAG and glucose concentrations. However, their genetic modulation by diet (dietary patterns or foods) remains to be investigated. We studied 945 high-cardiovascular risk subjects aged 67 (sd 6) years who participated in the PREvención con DIeta MEDiterránea-Valencia Study. Demographic, clinical, biochemical and genetic data were obtained. Adherence to the Mediterranean diet (MD) and food intake were measured by validated questionnaires. Carriers of the L allele of GKCR had significantly higher TAG concent…

First case in Italy of acquired resistance to oseltamivir in an immunocompromised patient with influenza A/H1N1v infection

2010

A pandemic influenza A/H1N1v strain with the neuraminidase H274Y mutation was detected in nasal secretions of a 2-year-old leukemic patient with influenza-like illness after 18 days of treatment with oseltamivir. At baseline, no drug-resistant virus was found, while 4 days after treatment initiation a mix- ture of wild-type and mutated virus was detected. After treatment interruption, the wild type influenza virus re-emerged and became prevalent in nasal secretions after a few days, suggesting the lower fitness of the mutated virus strain. The patient slowly improved concurrently with a decrease in virus load, which resulted negative 42 days after diagnosis. No other drug-resistant influenz…

Functional characterisation of alpha-galactosidase a mutations as a basis for a new classification system in fabry disease.

2013

Fabry disease (FD) is an X-linked hereditary defect of glycosphingolipid storage caused by mutations in the gene encoding the lysosomal hydrolase α-galactosidase A (GLA, α-gal A). To date, over 400 mutations causing amino acid substitutions have been described. Most of these mutations are related to the classical Fabry phenotype. Generally in lysosomal storage disorders a reliable genotype/phenotype correlation is difficult to achieve, especially in FD with its X-linked mode of inheritance. In order to predict the metabolic consequence of a given mutation, we combined in vitro enzyme activity with in vivo biomarker data. Furthermore, we used the pharmacological chaperone (PC) 1-deoxygalacto…