Search results for "Mutational analysis"
showing 10 items of 245 documents
Mutation analysis in myophosphorylase deficiency (McArdle's disease).
1998
Inherited deficiency of myophosphorylase leads to glycogen storage disease type V (McArdle's disease). We performed mutation analysis in 9 patients of eight unrelated families from Germany with typical cliniclal presentation of myophos-phorylase deficiency. Beside previously described mutations we identified four novel mutations in the myophorsphorylase gene. Four patients were homozygous for a nonsense mutation Arg49Stop that has been reported to be the most common mutation in white patients. Two affected siblings were compound heterozygotes for a novel missense mutation Gly685Arg and the nonsense mutation Arg49Stop. One patient carried a novel nonsense mutation Arg575Stop and a previously…
FUS mutations in sporadic amyotrophic lateral sclerosis
2011
Mutations in the FUS gene have recently been described as a cause of familial amyotrophic lateral sclerosis (ALS), but their role in the pathogenesis of sporadic ALS is unclear. We undertook mutational screening of all coding exons of FUS in 228 sporadic ALS cases, and, as previous reports suggest that exon 15 represents a mutational hotspot, we sequenced this exon in an additional 1295 sporadic cases. Six variants in six different cases were found, indicating that FUS mutations can underlie apparently sporadic ALS, but account for less than 1% of this form of disease. © 2010 .
Two Italian kindreds with familial amyotrophic lateral sclerosis due to FUS mutation
2009
Recently, fused in sarcoma/translated in liposarcoma (FUS/TLS) gene, located on chromosome 16p11.2, has been identified as a disease gene in familial amyotrophic lateral sclerosis (FALS). We have analyzed FUS/TLS in a cohort of 52 index cases from seven Italian regions with non-SOD1 and non-TARDBP FALS. We identified a heterozygous c.G1542C missense mutation in a family of northern Italian origin, and a heterozygous c.C1574T missense mutation in a family of Sicilian origin. Both variants are located in exon 15 encoding the RNA-recognition motif, and result in a substitution of an arginine with a serine in position 514 (p.R514S) and substitution of a proline with a leucine at position 525 (p…
Rapid and reliable genotyping procedure for detection of alleles with mutations, deletion, or/and duplication of the CYP2D6 gene
2009
Abstract Background Polymorphisms of cytochrome P450 2D6 (CYP2D6) have a significant effect on the pharmacokinetics of most tricyclic antidepressants. More than 150 alleles lead to four distinct phenotypes of drug metabolism. The phenotypes are described as ultrarapid, extensive, intermediate, and poor metabolizers. Therapeutic plasma levels of CYP2D6 substrates may be difficult to achieve. Here we describe a rapid and reliable procedure for CYP2D6*4, *3, *6, and *9 genotyping. Design and methods Serum concentrations of venlafaxine and its pharmacologically active metabolite, O-desmethylvenlafaxine, were measured in patients treated with the antidepressant venlafaxine, a substrate of CYP2D6…
BRCA1 genetic testing in 106 breast and ovarian cancer families from Southern Italy (Sicily): a mutation analyses.
2007
PURPOSE: To evaluate the contribution of germline BRCA1 mutations in the incidence of hereditary and familial Breast Cancer (BC) and/or Ovarian Cancer (OC) in patients from Southern Italy (in the region of Sicily) and to identify a possible association between the higher frequency of BRCA1 mutations and a specific familial profile. EXPERIMENTAL DESIGN: A consecutive series of 650 patients with BC and/or OC diagnosed between 1999 and 2005 were recruited from the Southern Italian region of Sicily, after interview at the "Regional Reference Centre for the Characterization and Genetic Screening of Hereditary Tumors" at the University of Palermo. Genetic counselling allowed us to recruit a total…
Oligophrenin 1 mutations frequently cause X-linked mental retardation with cerebellar hypoplasia
2005
Background: Mutations of oligophrenin 1, one of the first genes identified in nonspecific X-linked mental retardation (MRX), have been described in patients with moderate to severe cognitive impairment and predominant cerebellar hypoplasia, in the vermis. Objective: To further delineate the phenotypic and mutational spectrum of the syndrome, by screening oligophrenin 1 in two cohorts of male patients with mental retardation (MR) with or without known posterior fossa anomalies. Methods: Clinical examination, cognitive testing, MRI studies, and mutational analysis (denaturing gradient gel electrophoresis and direct sequencing) on blood lymphocytes were performed in 213 unrelated affected indi…
Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A/C gene.
2000
Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of the elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and life-threatening cardiomyopathy with conduction blocks. We recently identified LMNA encoding two nuclear envelope proteins, lamins A and C, to be implicated in the autosomal dominant form of EDMD. Here, we report on the variability of the phenotype and spectrum of LMNA mutations in 53 autosomal dominant EDMD patients (36 members of 6 families and 17 sporadic cases). Twelve of the 53 patients showed cardiac involvement exclusively, although the remaining 41 all showed muscle weakness and contractures. We were able to identify …
A novel mutation in the coagulation factor 12 gene in subjects with hereditary angioedema and normal C1-inhibitor.
2011
In hereditary angioedema with normal C1-inhibitor two different missense mutations of codon p.Thr328* in the coagulation factor 12 gene have been reported in some families. In this study a novel factor 12 gene mutation, the deletion of 72 base pairs (bp) (c.971_1018+24del72*), was identified in a family of Turkish origin, in two sisters with recurrent skin swellings and abdominal pain attacks and in their symptom-free father. This deletion caused a loss of 48 bp of exon 9 (coding amino acids 324* to 340*) in addition to 24 bp of intron 9, including the authentic donor splice site of exon 9. The large deletion of 72 bp was located in the same F12 gene region as the missense mutations p.Thr32…
Further evidence that D90A-SOD1 mutation is recessively inherited in ALS patients in Italy.
2008
Mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene have been reported to cause adult-onset autosomal dominant amyotrophic lateral sclerosis (FALS). In sporadic cases (SALS), de novo mutations in the SOD1 gene have occasionally been observed. All the SOD1 mutations are autosomal dominantly inherited with the exception of D90A. To date, in Italy, only two sporadic ALS cases carrying the D90A mutation have been reported in a homozygous state. We investigated for the presence of this mutation in 169 unrelated ALS patients from southern Italy. The genetic analysis revealed three ALS patients (1.8%) with mild phenotype carrying the homozygous D90A mutation.
Role of the pyrin M694V (A2080G) allele in acute myocardial infarction and longevity: a study in the Sicilian population
2006
Abstract A proinflammatory genotype seems to contribute significantly to the risk of developing coronary heart disease (CHD). Conversely, the susceptibility alleles to inflammatory disease should be infrequent in the genetic background favoring longevity. In fact, in a modern environment, attainment of longevity is facilitated by an anti-inflammatory status. To evaluate whether inflammatory alleles of pyrin, the gene responsible for familial Mediterranean fever (FMF) may play an opposite role in CHD and in longevity, we examined three FMF-associated mutations, M694V (A2080G), M694I (G2082A), and V726A (T2177C), encoded by the FMF gene (MEFV) in 121 patients affected by acute myocardial infa…