TY  - JOUR
AU  - Milašin, Jelena
AU  - Muntoni, F
AU  - Severini, GM
AU  - Bartoloni, L
AU  - Vatta, M
AU  - Krajinović, Maja
AU  - Mateddu, A
AU  - Angelini, C
AU  - Camerini, F
AU  - Falaschi, A
AU  - Mestroni, L
AU  - Giacca, M.
AU  - Pinamonti, B
AU  - Sinagra, G
AU  - Di Lenarda, A
AU  - Silvestri, F
AU  - Bussani, R
AU  - Davanzo, M
PY  - 1996
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1066
AB  - 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.
PB  - Oxford Univ Press United Kingdom, Oxford
T2  - Human Molecular Genetics
T1  - A point mutation in the 5' splice site of the dystrophin gene first intron responsible for X-linked dilated cardiomyopathy
VL  - 5
IS  - 1
SP  - 73
EP  - 79
DO  - 10.1093/hmg/5.1.73
ER  - 

@article{
author = "Milašin, Jelena and Muntoni, F and Severini, GM and Bartoloni, L and Vatta, M and Krajinović, Maja and Mateddu, A and Angelini, C and Camerini, F and Falaschi, A and Mestroni, L and Giacca, M. and Pinamonti, B and Sinagra, G and Di Lenarda, A and Silvestri, F and Bussani, R and Davanzo, M",
year = "1996",
abstract = "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.",
publisher = "Oxford Univ Press United Kingdom, Oxford",
journal = "Human Molecular Genetics",
title = "A point mutation in the 5' splice site of the dystrophin gene first intron responsible for X-linked dilated cardiomyopathy",
volume = "5",
number = "1",
pages = "73-79",
doi = "10.1093/hmg/5.1.73"
}

Milašin, J., Muntoni, F., Severini, G., Bartoloni, L., Vatta, M., Krajinović, M., Mateddu, A., Angelini, C., Camerini, F., Falaschi, A., Mestroni, L., Giacca, M., Pinamonti, B., Sinagra, G., Di Lenarda, A., Silvestri, F., Bussani, R.,& Davanzo, M.. (1996). A point mutation in the 5' splice site of the dystrophin gene first intron responsible for X-linked dilated cardiomyopathy. in Human Molecular Genetics
Oxford Univ Press United Kingdom, Oxford., 5(1), 73-79.
https://doi.org/10.1093/hmg/5.1.73

Milašin J, Muntoni F, Severini G, Bartoloni L, Vatta M, Krajinović M, Mateddu A, Angelini C, Camerini F, Falaschi A, Mestroni L, Giacca M, Pinamonti B, Sinagra G, Di Lenarda A, Silvestri F, Bussani R, Davanzo M. A point mutation in the 5' splice site of the dystrophin gene first intron responsible for X-linked dilated cardiomyopathy. in Human Molecular Genetics. 1996;5(1):73-79.
doi:10.1093/hmg/5.1.73 .

Milašin, Jelena, Muntoni, F, Severini, GM, Bartoloni, L, Vatta, M, Krajinović, Maja, Mateddu, A, Angelini, C, Camerini, F, Falaschi, A, Mestroni, L, Giacca, M., Pinamonti, B, Sinagra, G, Di Lenarda, A, Silvestri, F, Bussani, R, Davanzo, M, "A point mutation in the 5' splice site of the dystrophin gene first intron responsible for X-linked dilated cardiomyopathy" in Human Molecular Genetics, 5, no. 1 (1996):73-79,
https://doi.org/10.1093/hmg/5.1.73 . .