Improvement of low-density microelectronic array technology to characterize 14 mutations/single-nucleotide polymorphisms from several human genes on a large scale.

Sabrina Frusconi; Betti Giusti; Luciana Rossi; Sara Bernabini; Filippo Poggi; Irene Giotti; Rosanna Abbate; Guglielmina Pepe; Francesca Torricelli

doi:10.1373/clinchem.2003.025197

PubMed · 15044341

Improvement of low-density microelectronic array technology to characterize 14 mutations/single-nucleotide polymorphisms from several human genes on a large scale.

Sabrina Frusconi·Betti Giusti·Luciana Rossi·Sara Bernabini·Filippo Poggi·Irene Giotti·Rosanna Abbate·Guglielmina Pepe·Francesca Torricelli

View original source ↗Export metadata ↓

Abstract

The source did not provide an abstract. Follow the original record for more information.

Explore related subjects

Collagen Type VI Genotype Hemochromatosis Protein Histocompatibility Antigens Class I Humans Integrin alpha2 Integrin beta3 Membrane Proteins Mutation Oligonucleotide Array Sequence Analysis Polymerase Chain Reaction Polymorphism, Single Nucleotide Receptors, FSH Journal Article

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Sabrina Frusconi, Betti Giusti, Luciana Rossi, Sara Bernabini, Filippo Poggi, Irene Giotti, Rosanna Abbate, Guglielmina Pepe, Francesca Torricelli. 2004. Improvement of low-density microelectronic array technology to characterize 14 mutations/single-nucleotide polymorphisms from several human genes on a large scale.. https://doi.org/10.1373/clinchem.2003.025197

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2005

Collagen VI related muscle disorders.

Mutations in the genes encoding collagen VI (COL6A1, COL6A2, and COL6A3) cause Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), two conditions which were previously believed to be completely separate entities. BM is a relatively mild dominantly inherited disorder characterised by proximal weakness and distal joint contractures. UCMD was originally described as an autosomal recessive condition causing severe muscle weakness with proximal joint contractures and distal hyperlaxity. Here we review the clinical phenotypes of BM and UCMD and their diagnosis and management, and provide an overview of the current knowledge of the pathogenesis of collagen VI related disorders.

Collagen Type VI↗

PubMed2005

Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy.

INTRODUCTION: Mutations in the genes encoding collagen VI (COL6A1, COL6A2, and COL6A3) cause Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD). BM is a relatively mild dominantly inherited disorder with proximal weakness and distal joint contractures. UCMD is an autosomal recessive condition causing severe muscle weakness with proximal joint contractures and distal hyperlaxity. METHODS: We developed a method for rapid direct sequence analysis of all 107 coding exons of the COL6 genes using single condition amplification/internal primer (SCAIP) sequencing. We have sequenced all three COL6 genes from genomic DNA in 79 patients with UCMD or BM. RESULTS: We found putative mutations in one of the COL6 genes in 62% of patients. This more than doubles the number of identified COL6 mutations. Most of these changes are consistent with straightforward autosomal dominant or recessive inheritance. However, some patients showed changes in more than one of the COL6 genes, and our results suggest that some UCMD patients may have dominantly acting mutations rather than recessive disease. DISCUSSION: Our findings may explain some or all of the cases of UCMD that are unlinked to the COL6 loci under a recessive model. The large number of single nucleotide polymorphisms which we generated in the course of this work may be of importance in determining the major phenotypic variability seen in this group of disorders.

Collagen Type VI↗

PubMed2005

[Collagenopathy (Ullrich congenital muscular dystrophy, Bethlem myopathy)].

Collagenopathies with collagen VI mutations include Ullrich congenital muscular dystrophy (Ullrich's disease) and Bethlem myopathy. Patients with Ullrich's disease have generalized muscle weakness, multiple contractures of the proximal joints and hyperextensibility of the distal joints. Bethlem myopathy is characterized by the combination of proximal muscle weakness and contractures of finger, elbow, and ankle joints. We found for the first time a deficiency of collagen VI in Ullrich's disease. Furthermore, we found an abnormality of cell adhesion and abnormal regeneration or maturation in Ullrich's disease. Mutations in the genes COL6A1, COL6A2, COL6A3 are associated with Ullrich's disease and Bethlem myopathy. Bethlem myopathy is inherited in an autosomal dominant manner and Ullrich's disease usually in an autosomal recessive manner. Recently, de novo dominant mutations are reported in Ullrich's disease. We evaluated the role of nonsense-mediated mRNA decay (NMD) in Ullrich's disease that has a frameshift mutation with a premature termination codon in the COL6A2 gene causing the loss of collagen VI. The pharmacological block of NMD caused upregulation of the mutant collagen VI and partially functional extracellular matrix formation. Our results suggest that NMD inhibitors can be used as a therapeutic tool to rescue some human genetic diseases exacerbated by NMD.

Collagen Type VI↗