Search results for "Point Mutation"

Thirty-four novel mutations of the GLA gene in 121 patients with Fabry disease

2005

Fabry disease (FD) is an X-chromosomal disorder caused by mutations in the GLA gene encoding the lysosomal enzyme alpha-galactosidase A. We performed mutation screening on a cohort of 121 patients including 84 male and 37 female index cases and identified a total of 90 different mutations, 34 of which are reported for the first time here. Both point mutations (74.4%) and 'short length' rearrangements (25.6%) were found, including missense (54.4%), nonsense (14.4%), and splice site point mutations (5.6%), deletions (17.8%) or insertions/duplications (5.6%) of a few nucleotides, and complex rearrangements including larger deletions (2.2%). GLA mutations were identified in 82 (97.6%) of the 84…

A new polymorphism in the human HFE gene

1999

Mitochondrial DNA variations in patients with Type 2 (non-insulin dependent) diabetes mellitus and a Welsh control population

1999

The LDL-receptor gene point mutation FH-Genoa/Palermo is the most frequent mutation responsible for Familial Hypercholesterolemia in Sicily. The mutation does not introduce or abolish any useful restriction site. We establish a GeneComb-based strategy to identify this mutation in a population of Sicilian unrelated clinically diagnosed FH probands. The method was very sensitive and specific; 12 out of 90 (13.3%) unrelated FH probands were found to carry the FH-Genoa/Palermo mutation. According to these results, the FH-Genoa/Palermo is the more frequent LDL-receptor gene mutation among the Sicilian FH patients. Moreover FH-Genoa/Palermo is the mutation cluster to date more represented in Sout…

123 MOLECULAR GENETIC ANALYSIS IN HUNTER DISEASE

1991

Clinical and biochemical studies have revealed a great phenotypic variability in mucopolysaccharidosis type II (Hunter disease), probably due to different mutations in the IDS gene that has been localized in Xq28. Using a cDNA probe containing almost the entire coding region of the human IDS gene, we performed a molecular analysis on 7 patients with Hunter disease. In one patient, a complete deletion of the IDS coding sequences was found. Another patient had structural alterations of the IDS gene including a partial deletion. In 5 patients, however, after restriction digestion of the DNA by PstI and TaqI and Southern hybridization with the IDS cDNA, the audiographic patterns obtained were s…

Identification of Point Mutations in Genes Coding for tum-Antigens. A Step Towards the Understanding of Mouse and Human Tumor-Specific Transplantatio…

1989

Most experimental tumors induced with chemical carcinogens or UV radiation express individually specific transplantation antigens that elicit a T cell-mediated immune rejection in the syngeneic animals (Prehn and Main 1957; Klein et al. 1960; Kripke 1981; Uyttenhove et al. 1983). The characterization of these transplantation antigens has proved very difficult and several different approaches have been followed. One involves the search for specific antibodies to isolate the antigen by immunoprecipitation. Unfortunately, tumors seldom elicit antibodies directed against their specific transplantation antigens. One notable exception is UV-induced tumor 1591, and the molecules that were isolated…

Point Mutation Rate of Bacteriophage ΦX174

2009

Abstract The point mutation rate of phage ΦX174 was determined using the fluctuation test. After identifying the genetic changes associated with the selected phenotype, we obtained an estimate of 1.0 × 10−6 substitutions per base per round of copying, which is consistent with Drake's rule (0.003 mutations per genome per round of copying in DNA-based microorganisms).

In vitro genome editing using CRISPR/Cas9 to edit SERPINA1 PiZ mutation

2019

Introduction: The emergence some years ago of the CRISPR/Cas9 system allowed gene therapy to be specific, versatile, cheap and approachable to almost every laboratory. Due to these features, many different genetic diseases such as cystic fibrosis or β-thalassemia have been addressed in cellular models using the CRISPR/Cas9 genetic editing tool. Alpha-1 antytripsin deficiency (AATD) is a rare genetic condition that can provoke respiratory and hepatic symptoms. The Z allele of SERPINA1 gene is a well-characterised point mutation that can trigger the whole pathology. Henceforth, Z mutation is a suitable target for genetic edition using CRISPR/Cas9 in order to develop a gene therapy to treat AA…

New point mutation (R243W) in the hormone binding domain of the c‐erbA β1 gene in a family with generalized resistance to thyroid hormone

1996

Two years after the first mutation on exon 7 in the carboxy-terminal part of the hinge domain (D) was reported (Behr and Loos 1992), we have identified the second mutation on exon 7 in patients with GRTH. Interestingly, our mutation it is not located in the two previously described "hot spot regions", but instead very close to the hinge domain (D) of the receptor protein that is essential for the function of the hormone binding domain (E) (Lin et al., 1991). Confirming the observation that the majority of single base substitutions causing human genetic diseases or DNA polymorphisms follow the hot spot mutation rule of CG to TG and CG to CA transition (Barker et al., 1984), an additional CpG…

Deficiency of the Cockayne syndrome B (CSB) gene aggravates the genomic instability caused by endogenous oxidative DNA base damage in mice.

2007

The Cockayne syndrome B protein (CSB) has long been known to be involved in the repair of DNA modifications that block the RNA polymerase in transcribed DNA sequences (transcription-coupled repair). Recent evidence suggests that it also has a more general role in the repair of oxidative DNA base modifications such as 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxoG). In mammalian cells, 8-oxoG is a substrate of the repair glycosylase OGG1. Mice without this enzyme accumulate 8-oxoG in the genome and have elevated spontaneous mutation rates. To elucidate the role of CSB in the prevention of mutations by oxidative DNA base damage, we have generated mice that are deficient in Csb or Ogg1 or both ge…

Analysis of S-allele genetic diversity in Sicilian almond germplasm comparing different molecular methods

2015

Italian almond germplasm is characterized by a wide diversity in several growing areas among which Sicily is one of the most important. Analysis with consensus and specific primers and DNA sequencing was performed to investigate S-RNase genetic diversity and to elucidate the homology rate within a genetic pool of 27 Italian accessions. Interestingly, some of the self-compatible cultivars did not show the presence of Sf allele. Amplicons from consensus and allele-specific PCR primers revealed a high level of variability. Sequencing of all the S-RNase amplicons derived from consensus primers allowed the identification of two new S-RNase alleles (S51 and S52). Surprisingly, despite the AA repl…