Search results for "Mutational analysis"

Clinical application of mutational analysis in breast cancer patients: The relevance of PIK3CA analysis for precision medicine

2019

Abstract Background The identification of biomarkers to drive treatment is one of the most important objectives of precision medicine. During last years, the role of PIK3CA mutations have been related to clinical benefit deriving from treatment with PI3K, and mTOR inhibitors. In breast cancer (BC), PIK3CA mutations are widely present and the use, in clinical trials, of selective inhibitors improved clinical outcomes. The aim of this study is to assess the value of a monocentric genomic screening program to select patients for trials with experimental targeted agents. Methods We examined PIK3CA mutation in a cohort of 312 metastatic BC patients diagnosed at Hospital Clinico Valencia-INCLIVA …

Genotype and phenotype analysis of Friedreich's ataxia compound heterozygous patients

2000

Friedreich's ataxia is caused by mutations in the FRDA gene that encodes frataxin, a nuclear-encoded mitochondrial protein. Most patients are homozygous for the expansion of a GAA triplet repeat within the FRDA gene, but a few patients show compound heterozygosity for a point mutation and the GAA-repeat expansion. We analyzed DNA samples from a cohort of 241 patients with autosomal recessive or isolated spinocerebellar ataxia for the GAA triplet expansion. Patients heterozygous for the GAA expansion were screened for point mutations within the FRDA coding region. Molecular analyses included the single-strand conformation polymorphism analysis, direct sequencing, and linkage analysis with FR…

DJ-1 mutations and parkinsonism-dementia-amyotrophic lateral sclerosis complex.

2005

Mutations in DJ-1 gene have been recently shown to cause autosomal recessive early-onset Parkinson’s disease (EOPD) in a large Dutch family and in a small consanguineous Italian family.1 Subsequent to this initial finding, several additional DJ-1 mutations were identified in subjects with EOPD.2–6 We describe a family from southern Italy with three brothers affected by a complex disorder characterized by early-onset parkinsonism-dementia-amyotrophic lateral sclerosis (EOPD-D-ALS). The analysis of the DJ-1 gene showed a novel homozygous mutation (E163K) in exon 7 and a novel homozygous mutation (g.168_185dup) in the promoter region of this gene in living affected subjects

RNA sequencing-based transcriptome profiling of cardiac tissue Implicados novela putative disease mechanisms in FLNC-associated arrhythmogenic cardio…

2020

Arrhythmogenic cardiomyopathy (ACM) encompasses a group of inherited cardiomyopathies including arrhythmogenic right ventricular cardiomyopathy (ARVC) whose molecular disease mechanism is associated with dysregulation of the canonical WNT signalling pathway. Recent evidence indicates that ARVC and ACM caused by pathogenic variants in the FLNC gene encoding filamin C, a major cardiac structural protein, may have different molecular mechanisms of pathogenesis. We sought to identify dysregulated biological pathways in FLNC-associated ACM. RNA was extracted from seven paraffin-embedded left ventricular tissue samples from deceased ACM patients carrying FLNC variants and sequenced. Transcript le…

Identification of two new mutations in TRPS 1 gene leading to the tricho-rhino-phalangeal syndrome type I and III.

2009