caa a22 4500 397575157 CHVBK 20180308164853.0 cr unu---uuuuu 161202e199611 xx s 000 0 eng 10.1093/hmg/5.11.1841 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.11.1841 Mutations That Disrupt the Carboxyl-Terminus of γ-Sarcoglycan Cause Muscular Dystrophy [Elektronische Daten] [Elizabeth M. McNally, David Duggan, J. Rafael Gorospe, Carsten G. Bönnemann, Marina Fanin, Elena Pegoraro, Hart G. W. Lidov, Satoru Noguchi, Eijiro Ozawa, Richard S. Finkel, Robert P. Cruse, Corrado Angelini, Louis M. Kunkel, Eric P. Hoffman] Recently, mutations in the genes encoding several of the dystrophin-associated proteins have been identified that produce phenotypes ranging from severe Duchenne-like autosomal recessive muscular dystrophy to the milder limb-girdle muscular dystrophies (LGMDs). LGMD type 2C is generally associated with a more severe clinical course and is prevalent in northern Africa. A previous study identified a single base pair deletion in the gene encoding the dys-trophin-associated protein γ-sarcoglycan in a number of Tunisian muscular dystrophy patients. To investigate whether γ-sarcoglycan gene mutations cause autosomal recessive muscular dystrophy in other populations, we studied 50 muscular dystrophy patients from the United States and Italy. The muscle biopsies from these 50 patients showed no abnormality of dystrophin but did show diminished immunostaining for the dystrophin-associated protein α-sarcoglycan. Four patients with a severe muscular dystrophy phenotype were identified with homozygous, frameshifting mutations in γ-sarcoglycan. Two of the four have microdele-tions that disrupt the distal carboxyl-terminus of γ-sarcoglycan yet result in a complete absence of γ- and β-sarcoglycan suggesting the importance of this region for stability of the sarcoglycan complex. This region of γ-sarcoglycan, like β-sarcoglycan, has a number of cysteine residues similar to those in epidermal growth factor cysteine-rich regions. © 1996 Oxford University Press McNally Elizabeth M. Division of Genetics and the Howard Hughes Medical Institute, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA aut Duggan David Departments of Human Genetics, Molecular Genetics and Biochemistry, Pediatrics and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 USA aut Rafael Gorospe J. Departments of Human Genetics, Molecular Genetics and Biochemistry, Pediatrics and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 USA aut Bönnemann Carsten G. Division of Genetics and the Howard Hughes Medical Institute, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA aut Fanin Marina Clinica Neurologica 1, Universita di Padova, 35128 Padova, Italy aut Pegoraro Elena Departments of Human Genetics, Molecular Genetics and Biochemistry, Pediatrics and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 USA aut Lidov Hart G. W. Division of Genetics and the Howard Hughes Medical Institute, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA aut Noguchi Satoru Department of Cell Biology, National Institute of Neuroscience, National Center for Neurology and Psychiatry, Kodaira, Tokyo 187, Japan aut Ozawa Eijiro Department of Cell Biology, National Institute of Neuroscience, National Center for Neurology and Psychiatry, Kodaira, Tokyo 187, Japan aut Finkel Richard S. Muscle Clinic, Division of Child Neurology, Departments of Pediatrics and Neurology, University of Colorado Health Sciences Center, The Children's Hospital, Denver, CO 80218 USA aut Cruse Robert P. Pediatric Neurology, Peoria, IL 61603 USA aut Angelini Corrado Clinica Neurologica 1, Universita di Padova, 35128 Padova, Italy aut Kunkel Louis M. Division of Genetics and the Howard Hughes Medical Institute, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA aut Hoffman Eric P. Departments of Human Genetics, Molecular Genetics and Biochemistry, Pediatrics and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 USA aut Human Molecular Genetics Oxford University Press 5/11(1996-11), 1841-1847 0964-6906 5:11<1841 1996 5 hmg https://doi.org/10.1093/hmg/5.11.1841 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.11.1841 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- McNally Elizabeth M. Division of Genetics and the Howard Hughes Medical Institute, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA aut NATIONALLICENCE 700 1- Duggan David Departments of Human Genetics, Molecular Genetics and Biochemistry, Pediatrics and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 USA aut NATIONALLICENCE 700 1- Rafael Gorospe J. Departments of Human Genetics, Molecular Genetics and Biochemistry, Pediatrics and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 USA aut NATIONALLICENCE 700 1- Bönnemann Carsten G. Division of Genetics and the Howard Hughes Medical Institute, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA aut NATIONALLICENCE 700 1- Fanin Marina Clinica Neurologica 1, Universita di Padova, 35128 Padova, Italy aut NATIONALLICENCE 700 1- Pegoraro Elena Departments of Human Genetics, Molecular Genetics and Biochemistry, Pediatrics and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 USA aut NATIONALLICENCE 700 1- Lidov Hart G. W. Division of Genetics and the Howard Hughes Medical Institute, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA aut NATIONALLICENCE 700 1- Noguchi Satoru Department of Cell Biology, National Institute of Neuroscience, National Center for Neurology and Psychiatry, Kodaira, Tokyo 187, Japan aut NATIONALLICENCE 700 1- Ozawa Eijiro Department of Cell Biology, National Institute of Neuroscience, National Center for Neurology and Psychiatry, Kodaira, Tokyo 187, Japan aut NATIONALLICENCE 700 1- Finkel Richard S. Muscle Clinic, Division of Child Neurology, Departments of Pediatrics and Neurology, University of Colorado Health Sciences Center, The Children's Hospital, Denver, CO 80218 USA aut NATIONALLICENCE 700 1- Cruse Robert P. Pediatric Neurology, Peoria, IL 61603 USA aut NATIONALLICENCE 700 1- Angelini Corrado Clinica Neurologica 1, Universita di Padova, 35128 Padova, Italy aut NATIONALLICENCE 700 1- Kunkel Louis M. Division of Genetics and the Howard Hughes Medical Institute, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA aut NATIONALLICENCE 700 1- Hoffman Eric P. Departments of Human Genetics, Molecular Genetics and Biochemistry, Pediatrics and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/11(1996-11), 1841-1847 0964-6906 5:11<1841 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