caa a22 4500 397575661 CHVBK 20180308164855.0 cr unu---uuuuu 161202e199612 xx s 000 0 eng 10.1093/hmg/5.12.1953 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.12.1953 Genomic Screening for β-Sarcoglycan Gene Mutations: Missense Mutations May Cause Severe Limb-girdle Muscular Dystrophy Type 2E (LGMD 2E) [Elektronische Daten] [Carsten G. Bönnemann, M. Rita Passos-Bueno, Elizabeth M. McNally, Mariz Vainzof, Eloísa de Sá Moreira, Suely K. Marie, Rita C. M. Pavanello, Satoru Noguchi, Eijiro Ozawa, Mayana Zatz, Louis M. Kunkel] Autosomal recessive limb-girdle muscular dystrophies (LGMDs) are genetically heterogeneous. A subgroup of these disorders is caused by mutations in the dystrophin-associated sarcoglycan complex. Truncating mutations in the 43 kDa β-sarcoglycan gene (LGMD 2E) were originally identified in a sporadic case of Duchenne-like muscular dystrophy, and a common missense mutation (T151R) was identified independently in Indiana Amish pedigrees with a milder form of LGMD. To facilitate mutational analysis of larger numbers of patients directly from genomic DNA, as opposed to reverse transcribed RNA from muscle biopsies, we have determined the genomic structure of the β-sarcoglycan gene. The open reading frame of the β-sarcoglycan coding region extends over six exons. Primers were designed for PCR amplification of single exons from genomic DNA and subsequent single strand conformation polymorphism (SSCP) analysis. We screened 15 patients from the Brazilian LGMD patient population, 13 of whom followed a severe course. Most of the patients had been assessed previously for deficiency of α-sarcoglycan immunofluorescence on muscle biopsy sections as a marker for disease of the sarcoglycan complex. Novel mutations in two familial and two sporadic cases of severe childhood-onset LGMD were identified. Only one of these patients carried a truncating mutation (homozygous 2 bp deletion, FS164TER), while the other three carried missense mutations (homozygous R91P, homozygous M100K, heterozygous recessive L108R; only one allele could be identified in this family). All three missense mutations occurred in exon 3, coding for the immediate extracellular domain. Complete absence for all three of the known sarcoglycans was noted by immunohistochemistry on muscle biopsy sections of the patients. © 1993 Oxford University Press Bönnemann Carsten G. Howard Hughes Medical Institute and Division of Genetics, Boston, MA 02115, USA aut Passos-Bueno M. Rita Departamento di Biologia, Instituto de Biosciências, Universidade de São Paulo, CEP 05508-900 São Paulo, Brazil aut McNally Elizabeth M. Howard Hughes Medical Institute and Division of Genetics, Boston, MA 02115, USA aut Vainzof Mariz Department of Neurology, Children's Hospital, and Harvard Medical School, Boston, MA 02115, USA aut Moreira Eloísa de Sá Departamento di Biologia, Instituto de Biosciências, Universidade de São Paulo, CEP 05508-900 São Paulo, Brazil aut Marie Suely K. Departamento de Neurologia, Faculdade de Medicina, Universidade de São Paulo, CEP 05508-900 São Paulo, Brazil aut Pavanello Rita C. M. Departamento di Biologia, Instituto de Biosciências, Universidade de São Paulo, CEP 05508-900 São Paulo, Brazil aut Noguchi Satoru National Institute of Neuroscience, Kodaira, Tokyo 187, Japan aut Ozawa Eijiro National Institute of Neuroscience, Kodaira, Tokyo 187, Japan aut Zatz Mayana Departamento di Biologia, Instituto de Biosciências, Universidade de São Paulo, CEP 05508-900 São Paulo, Brazil aut Kunkel Louis M. Howard Hughes Medical Institute and Division of Genetics, Boston, MA 02115, USA aut Human Molecular Genetics Oxford University Press 5/12(1996-12), 1953-1961 0964-6906 5:12<1953 1996 5 hmg https://doi.org/10.1093/hmg/5.12.1953 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.12.1953 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bönnemann Carsten G. Howard Hughes Medical Institute and Division of Genetics, Boston, MA 02115, USA aut NATIONALLICENCE 700 1- Passos-Bueno M. Rita Departamento di Biologia, Instituto de Biosciências, Universidade de São Paulo, CEP 05508-900 São Paulo, Brazil aut NATIONALLICENCE 700 1- McNally Elizabeth M. Howard Hughes Medical Institute and Division of Genetics, Boston, MA 02115, USA aut NATIONALLICENCE 700 1- Vainzof Mariz Department of Neurology, Children's Hospital, and Harvard Medical School, Boston, MA 02115, USA aut NATIONALLICENCE 700 1- Moreira Eloísa de Sá Departamento di Biologia, Instituto de Biosciências, Universidade de São Paulo, CEP 05508-900 São Paulo, Brazil aut NATIONALLICENCE 700 1- Marie Suely K. Departamento de Neurologia, Faculdade de Medicina, Universidade de São Paulo, CEP 05508-900 São Paulo, Brazil aut NATIONALLICENCE 700 1- Pavanello Rita C. M. Departamento di Biologia, Instituto de Biosciências, Universidade de São Paulo, CEP 05508-900 São Paulo, Brazil aut NATIONALLICENCE 700 1- Noguchi Satoru National Institute of Neuroscience, Kodaira, Tokyo 187, Japan aut NATIONALLICENCE 700 1- Ozawa Eijiro National Institute of Neuroscience, Kodaira, Tokyo 187, Japan aut NATIONALLICENCE 700 1- Zatz Mayana Departamento di Biologia, Instituto de Biosciências, Universidade de São Paulo, CEP 05508-900 São Paulo, Brazil aut NATIONALLICENCE 700 1- Kunkel Louis M. Howard Hughes Medical Institute and Division of Genetics, Boston, MA 02115, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/12(1996-12), 1953-1961 0964-6906 5:12<1953 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