caa a22 4500 397575238 CHVBK 20180308164854.0 cr unu---uuuuu 161202e199601 xx s 000 0 eng 10.1093/hmg/5.1.73 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.1.73 A Point Mutation in the 5′ Splice Site of the Dystrophin Gene First Intron Responsible for X-Linked Dilated Cardiomyopathy [Elektronische Daten] [Jelena Milasin, Francesco Muntoni, Giovanni Maria Severini, Lucia Bartoloni, Matteo Vatta, Maja Krajinovic, Anna Mateddu, Corrado Angelini, Fulvio Camerini, Arturo Falaschi, Luisa Mestroni, Mauro Giacca] X-linked dilated cardiomyopathy (XLDC) is a familial heart disease presenting in young males as a rapidly progressive congestive heart failure, without clinical signs of skeletal myopathy. This condition has recently been linked to the dystrophin gene in some families and deletions encompassing the genomic region coding for the first muscle exon have been detected. In order to identify the defect responsible for this disease at the molecular level and to understand the reasons for the selective heart involvement, a family with a severe form of XLDC was studied. In the affected members, no deletions of the dystrophin gene were observed. Analysis of the muscle promoter, first exon and intron regions revealed the presence of a single point mutation at the first exon-intron boundary, inactivating the universally conserved 5′ splice site consensus sequence of the first intron. This mutation introduced a new restriction site for Msel, which cosegregates with the disease in the analyzed family. Expression of the major dystrophin mRNA isoforms (from the muscle-, brain- and Purkinje cell-promoters) was completely abolished in the myocardium, while the brain- and Purkinje cell- (but not the muscle-) isoforms were detectable in the skeletal muscle. Immunocytochemical studies with anti-dystrophin antibodies showed that the protein was reduced in quantity but normally distributed in the skeletal muscle, while it was undetectable in the cardiac muscle. These findings indicate that expression of the muscle dystrophin isoform is critical for myocardial function and suggest that selective heart involvement in dystrophin-linked dilated cardiomyopathy is related to the absence, in the heart, of a compensatory expression of dystrophin from alternative promoters. © 1996 Oxford University Press Milasin Jelena International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy aut Muntoni Francesco Department of Pediatrics and Neonatal Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 0NN, UK aut Maria Severini Giovanni International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy aut Bartoloni Lucia Department of Biology and Neurology, University of Padova, 35121 Padova, Italy aut Vatta Matteo International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy aut Krajinovic Maja International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy aut Mateddu Anna Department of Neuroscience, University of Cagliari, 09100 Cagliari, Italy aut Angelini Corrado Department of Biology and Neurology, University of Padova, 35121 Padova, Italy aut Camerini Fulvio Department of Cardiology, Ospedale Maggiore and University of Trieste, 34100 Trieste, Italy aut Falaschi Arturo International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy aut Mestroni Luisa International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy aut Giacca Mauro International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy aut Human Molecular Genetics Oxford University Press 5/1(1996-01), 73-79 0964-6906 5:1<73 1996 5 hmg https://doi.org/10.1093/hmg/5.1.73 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.1.73 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Milasin Jelena International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy aut NATIONALLICENCE 700 1- Muntoni Francesco Department of Pediatrics and Neonatal Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 0NN, UK aut NATIONALLICENCE 700 1- Maria Severini Giovanni International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy aut NATIONALLICENCE 700 1- Bartoloni Lucia Department of Biology and Neurology, University of Padova, 35121 Padova, Italy aut NATIONALLICENCE 700 1- Vatta Matteo International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy aut NATIONALLICENCE 700 1- Krajinovic Maja International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy aut NATIONALLICENCE 700 1- Mateddu Anna Department of Neuroscience, University of Cagliari, 09100 Cagliari, Italy aut NATIONALLICENCE 700 1- Angelini Corrado Department of Biology and Neurology, University of Padova, 35121 Padova, Italy aut NATIONALLICENCE 700 1- Camerini Fulvio Department of Cardiology, Ospedale Maggiore and University of Trieste, 34100 Trieste, Italy aut NATIONALLICENCE 700 1- Falaschi Arturo International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy aut NATIONALLICENCE 700 1- Mestroni Luisa International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy aut NATIONALLICENCE 700 1- Giacca Mauro International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/1(1996-01), 73-79 0964-6906 5:1<73 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford