Search results for "Point mutation"

A novel mutation in FGFR-3 disrupts a putative N-glycosylation site and results in hypochondroplasia

2000

Winterpacht, Andreas, Katja Hilbert, Christiane Stelzer, Thorsten Schweikardt, Heinz Decker, Hugo Segerer, Jürgen Spranger, and Bernhard Zabel. A novel mutation in FGFR-3 disrupts a putative N-glycosylation site and results in hypochondroplasia. Physiol. Genomics 2: 9–12, 2000.—Fibroblast growth factor receptor 3 (FGFR3) is a glycoprotein that belongs to the family of tyrosine kinase receptors. Specific mutations in the FGFR3 gene are associated with autosomal dominant human skeletal disorders such as hypochondroplasia, achondroplasia, and thanatophoric dysplasia. Hypochondroplasia (HCH), the mildest form of this group of short-limbed dwarfism disorders, results in ∼60% of cases from a mut…

tert-Butoxyl radicals generate mainly 7,8-dihydro-8-oxoguanine in DNA.

2000

Abstract Like hydroxyl radicals, alkoxyl radicals have been implicated in the generation of cellular oxidative DNA damage under physiological conditions; however, their genotoxic potential has not yet been established. We have analyzed the DNA damage induced by a photochemical source of tert- butoxyl radicals, the water soluble peroxy ester [4-( tert -butyldioxycarbonyl)benzyl]triethylammonium chloride (BCBT), using various repair endonucleases as probes. The irradiation (UV 360 ) of BCBT in the presence of bacteriophage PM2 DNA was found to generate a DNA damage profile that consisted mostly of base modifications sensitive to the repair endonuclease Fpg protein. Approximately 90% of the mo…

High prevalence to resistance of clarithromycin in Helicobacter pylori strains isolated in Sicily .

2012

Mutation specific PCR and direct solid phase sequencing assay for the detection of hepatitis B virus pre-C/C mutants in anti-HBe-positive, chronic he…

1994

Sequence analysis of the HBV DNA from patients with anti-HBe+, chronic hepatitis B revealed that the lack of HBeAg is mostly due to a single GA transition at nucleotide position 1896, resulting in a translational stop codon. A point mutation-specific polymerase chain reaction (msPCR) for the detection of this genetic variant was established. Two serologically defined groups of patients with symptomatic chronic hepatitis B (HBeAg+ n = 14, anti-HBe+ n = 11) were included in this study. Viral DNA from 43 sera (26 eAg+/17 anti-HBe+) was amplified twice, using two different sets of PCR primers. Each set contained the same — strand primer, but the + strand primers differed at their 3′-end, thus b…

Semiquantitative assessment of pre-core stop-codon mutant and wildtype hepatitis B virus during the course of chronic hepatitis B using a new PCR-bas…

1996

In most patients with chronic hepatitis B positive for antibodies (anti-HBe) to HBe antigen (HBeAg), a pre-core mutant hepatitis B virus (HBV) with a point-mutation at nt. 1896 can be isolated. Clinical significance of the mutant virus in chronic hepatitis B is not proven yet, and screening of large numbers of sera during different clinical courses of numerous patients is necessary. We therefore aimed to develop a fast and reliable assay, that allows to discriminate wildtype from nt. 1896 G-->A mutant HBV and to determine the ratio of mutant and wildtype HBV in patients' sera. A mutation specific polymerase chain reaction (ms PCR) with new primers served to distinguish nt. 1896 G-->A mutant…

Hereditäre Pankreatitis - Eine klinisch relevante Ursache des Pankreaskarzinoms? -

2001

UNLABELLED Hereditary pancreatitis is an autosomal dominant disease. Recently, the genetic defect has been mapped to chromosome 7q35 and consists mainly of a point mutation in exon 3 of the cationic trypsinogen gene which causes an Arg(CGC)-His(CAC) substitution at residue 117. In patients with hereditary pancreatitis the estimated cumulative risk for pancreatic carcinoma to age 70 approaches 40 %. Thus, the role of hereditary pancreatitis in the pathogenesis of pancreatic carcinoma is of interest. PATIENTS AND METHODS DNA was extracted from peripheral blood (n = 16), fresh tumor tissue (n = 29) and formalin fixed and paraffin embedded tumor tissue (n = 5) of 50 patients with ductal adenoca…

Amino acid substitutions enhancing thermostability of Bacillus polymyxa beta-glucosidase A

1996

Mutations enhancing the thermostability of β-glucosidase A of Bacillus polymyxa, a family 1 glycosyl hydrolase, have been obtained after hydroxylamine mutagenesis of a plasmid containing the bglA gene, transformation of Escherichia coli with the mutagenized plasmid, and identification of transformant colonies that showed β-glucosidase activity after a thermal treatment that inactivated the wild-type enzyme. Two additive mutations have been characterized that cause replacement of glutamate at position 96 by lysine and of methionine at position 416 by isoleucine respectively. The thermoresistant mutant enzymes showed increased resistance to other denaturing agents, such as pH and urea, while …

AML-associated Flt3 kinase domain mutations show signal transduction differences compared with Flt3 ITD mutations

2005

Activating mutations of Flt3 are found in approximately one third of patients with acute myeloid leukemia (AML) and are an attractive drug target. Two classes of Flt3 mutations occur: internal tandem duplications (ITDs) in the juxtamembrane and point mutations in the tyrosine kinase domain (TKD). We and others have shown that Flt3-ITD induced aberrant signaling including strong activation of signal transducer and activator of transcription 5 (STAT5) and repression of CCAAT/estradiol-binding protein α (c/EBPα) and Pu.1. Here, we compared the signaling properties of Flt3-ITD versus Flt3-TKD in myeloid progenitor cells. We demonstrate that Flt3-TKD mutations induced autonomous growth of 32D ce…

Molecular basis of filamin a-filGAP interaction and its impairment in congenital disorders associated with filamin a mutations

2008

Background Mutations in filamin A (FLNa), an essential cytoskeletal protein with multiple binding partners, cause developmental anomalies in humans. Methodology/Principal Findings We determined the structure of the 23rd Ig repeat of FLNa (IgFLNa23) that interacts with FilGAP, a Rac-specific GTPase-activating protein and regulator of cell polarity and movement, and the effect of the three disease-related mutations on this interaction. A combination of NMR structural analysis and in silico modeling revealed the structural interface details between the C and D β-strands of the IgFLNa23 and the C-terminal 32 residues of FilGAP. Mutagenesis of the predicted key interface residues confirmed the b…

Paramagnetic Cobalt and Nickel Derivatives of Alcaligenes denitrificans Azurin and Its M121Q Mutant. A 1H NMR Study

1996

Using cobalt or nickel to replace copper in native azurin allows one to fingerprint the metal coordination site of the protein. The metal sites of wild type Alcaligenes denitrificans azurin and its M121Q mutant are clearly distinguishable through the paramagnetic 1H NMR spectra of the Ni(II) and Co(II) derivatives. In the wild type azurin, Gly45 coordinates to nickel or cobalt, while Met121 appears as a weak metal ligand. On the contrary, in the M121Q azurin mutant, the metal exhibits a clear preference for the Gln121, which coordinates through the side chain carbonyl oxygen, and Gly45 is not a ligand. Changes in the isotropic shifts and relaxation properties of signals from the Cys112, His…