Search results for "gene mutation"

Desmin‐related Myopathies

2006

Outstanding progress in elucidating the pathology of muscular disorders at light and electron microscopic levels has allowed the identification of proteins involved in pathological alterations. This, in turn, has led to discoveries of multiple genes and mutations associated with previously poorly understood conditions. An unexpected result is that phenotypically similar and pathogenetically related neuromuscular disorders are associated with mutations in one or the other of several interacting proteins. Keywords: desmin-related myopathy; distal myopathy; cardiomyopathy; desmin and alpha-B crystallin gene mutations; functional analysis; molecular pathogenesis; genotype–phenotype correlations

Detection of mammalian carcinogens with an immunological DNA synthesis-inhibition test.

1992

There is a close relationship between genotoxicity, mutagenicity and carcinogenicity. But the controversy of which short-term test system best recognizes human carcinogens is still going on. Currently, the Salmonella gene mutation assay ('Ames test') is the most widely used test for the screening of mutagens. However, many in vitro tests hold unsatisfactory validity data, presumably because of the inability of present short-term tests to detect non-genotoxic carcinogens, which are increasingly being brought into focus in the discussions of genesis of cancer. One principle often neglected in this context is the property of genotoxic agents to inhibit replicative DNA synthesis in (proliferati…

Laser Pressure Catapulting (LPC): Optimization LPC-System and Genotyping of Colorectal Carcinomas

2005

Genotype analysis is becoming more and more useful in clinical practice, since specific mutations in tumors often correlate with prognosis and/or therapeutic response. Unfortunately, current molecular analytical techniques often require time-consuming and costly steps of analysis, thus making their routine clinical use difficult. Moreover, one of the most difficult problems arising during tumor research is that of their cell heterogeneity, which depends on their clear molecular heterogeneity. SSCP analysis discriminates by means of aberrant electrophoresis migration bands, mutated alleles which may represent as little as 15-20% of their total number. Nevertheless, in order to identify by se…

Molecular Genetic Investigations in Autosomal Dominant Polycystic Kidney Disease. Gene Mutation Detection, Linkage Analysis, and Preliminary ACE Gene…

1997

Systematic screening for mutations in the human serotonin 1F receptor gene in patients with bipolar affective disorder and schizophrenia

1996

Using single strand conformational analysis we screened the complete coding sequence of the serotonin 1F (5-HT{sub 1F}) receptor gene for the presence of DNA sequence variation in a sample of 137 unrelated individuals including 45 schizophrenic patients, 46 bipolar patients, as well as 46 healthy controls. We detected only three rare sequence variants which are characterized by single base pair substitutions, namely a silent T{r_arrow}A transversion in the third position of codon 261 (encoding isoleucine), a silent C{r_arrow}T transition in the third position of codon 176 (encoding histidine), and a C{r_arrow}T transition in position -78 upstream from the start codon. The lack of significan…

Identification of novel SLC3A1 gene mutations in Spanish cystinuria families and association with clinical phenotypes

2004

Cystinuria is an inherited metabolic disease characterized by an abnormal urinary excretion of cystine and dibasic amino acids, leading to kidney stone formation. Incidence of cystinuria in the Mediterranean Spanish population is one of the highest in the world. In view of the low prevalence of previously reported mutations in the SLC3A1 gene, analyses to identify novel variants were carried out on 20 cystinuria families. Additionally, we investigated the possible association between these molecular variants and clinical phenotypes. Genomic DNA from 48 cystinuria patients, 44 healthy relatives and 81 unrelated controls from the East Mediterranean coast of Spain was screened by conformation …

A total of 220 patients with autosomal dominant spastic paraplegia do not display mutations in the SLC33A1 gene (SPG42).

2010

The most frequent causes of autosomal dominant (AD) hereditary spastic paraplegias (HSP) (ADHSP) are mutations in the SPAST gene (SPG4 locus). However, roughly 60% of patients are negative for SPAST mutations, despite their family history being compatible with AD inheritance. A mutation in the gene for an acetyl-CoA transporter (SLC33A1) has recently been reported in one Chinese family to cause ADHSP-type SPG42. In this study, we screened 220 independent SPAST mutation-negative ADHSP samples for mutations in the SLC33A1 gene by high-resolution melting curve analysis. Conspicuous samples were validated by direct sequencing. Moreover, copy number variations affecting SLC33A1 were screened by …

Intermediate Filament Diseases: Desminopathy

2008

Desminopathy is one of the most common intermediate filament human disorders associated with mutations in closely interacting proteins, desmin and alphaB-crystallin. The inheritance pattern in familial desminopathy is characterized as autosomal dominant or autosomal recessive, but many cases have no family history. At least some and likely most sporadic desminopathy cases are associated with de novo DES mutations. The age of disease onset and rate of progression may vary depending on the type of inheritance and location of the causative mutation. Typically, the illness presents with lower and later upper limb muscle weakness slowly spreading to involve truncal, neck-flexor, facial and bulba…

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…

Systematic screening for mutations in the promoter and the coding region of the 5-HT1A gene.

1995

In the present study we sought to identify genetic variation in the 5-HT{sub 1A} receptor gene which through alteration of protein function or level of expression might contribute to the genetic predisposition to neuropsychiatric diseases. Genomic DNA samples from 159 unrelated subjects (including 45 schizophrenic, 46 bipolar affective, and 43 patients with Tourette`s syndrome, as well as 25 healthy controls) were investigated by single-strand conformation analysis. Overlapping PCR (polymerase chain reaction) fragments covered the whole coding sequence as well as the 5{prime} untranslated region of the 5-HT{sub 1A} gene. The region upstream to the coding sequence we investigated contains a …