PubMed:22453924 JSONTXT

{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":768,"end":771},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000604"}],"text":"Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes protein misfolding and mild Becker muscular dystrophy.\nMutations in the dystrophin gene without disruption of the reading frame often lead to Becker muscular dystrophy, but a genotype/phenotype correlation is difficult to establish. Amino acid substitutions may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two brothers (ages 8 and 10 years) with very mild proximal weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin gene (c.1280T\u003eC) leading to a L427P amino acid substitution in repeat 1 of the central rod domain. Immunostaining of skeletal muscle showed weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial misfolding of the L427P mutated protein as well as a reduced refolding rate after denaturation. Based on computational homology models of the wild-type and mutated R1-2, a molecular dynamics study showed an alteration in the flexibility of the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this missense mutation hinders the dynamic properties of the entire N-terminal region of dystrophin."}

{"project":"sentences","denotations":[{"id":"TextSentencer_T1","span":{"begin":0,"end":131},"obj":"Sentence"},{"id":"TextSentencer_T2","span":{"begin":132,"end":309},"obj":"Sentence"},{"id":"TextSentencer_T3","span":{"begin":310,"end":441},"obj":"Sentence"},{"id":"TextSentencer_T4","span":{"begin":442,"end":609},"obj":"Sentence"},{"id":"TextSentencer_T5","span":{"begin":610,"end":779},"obj":"Sentence"},{"id":"TextSentencer_T6","span":{"begin":780,"end":975},"obj":"Sentence"},{"id":"TextSentencer_T7","span":{"begin":976,"end":1172},"obj":"Sentence"},{"id":"TextSentencer_T8","span":{"begin":1173,"end":1436},"obj":"Sentence"},{"id":"TextSentencer_T9","span":{"begin":1437,"end":1562},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":131},"obj":"Sentence"},{"id":"T2","span":{"begin":132,"end":309},"obj":"Sentence"},{"id":"T3","span":{"begin":310,"end":441},"obj":"Sentence"},{"id":"T4","span":{"begin":442,"end":609},"obj":"Sentence"},{"id":"T5","span":{"begin":610,"end":779},"obj":"Sentence"},{"id":"T6","span":{"begin":780,"end":975},"obj":"Sentence"},{"id":"T7","span":{"begin":976,"end":1172},"obj":"Sentence"},{"id":"T8","span":{"begin":1173,"end":1436},"obj":"Sentence"},{"id":"T9","span":{"begin":1437,"end":1562},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes protein misfolding and mild Becker muscular dystrophy.\nMutations in the dystrophin gene without disruption of the reading frame often lead to Becker muscular dystrophy, but a genotype/phenotype correlation is difficult to establish. Amino acid substitutions may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two brothers (ages 8 and 10 years) with very mild proximal weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin gene (c.1280T\u003eC) leading to a L427P amino acid substitution in repeat 1 of the central rod domain. Immunostaining of skeletal muscle showed weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial misfolding of the L427P mutated protein as well as a reduced refolding rate after denaturation. Based on computational homology models of the wild-type and mutated R1-2, a molecular dynamics study showed an alteration in the flexibility of the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this missense mutation hinders the dynamic properties of the entire N-terminal region of dystrophin."}

{"project":"Glycosmos6-MAT","denotations":[{"id":"T1","span":{"begin":511,"end":519},"obj":"http://purl.obolibrary.org/obo/MAT_0000491"},{"id":"T2","span":{"begin":798,"end":813},"obj":"http://purl.obolibrary.org/obo/MAT_0000302"},{"id":"T3","span":{"begin":807,"end":813},"obj":"http://purl.obolibrary.org/obo/MAT_0000025"}],"text":"Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes protein misfolding and mild Becker muscular dystrophy.\nMutations in the dystrophin gene without disruption of the reading frame often lead to Becker muscular dystrophy, but a genotype/phenotype correlation is difficult to establish. Amino acid substitutions may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two brothers (ages 8 and 10 years) with very mild proximal weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin gene (c.1280T\u003eC) leading to a L427P amino acid substitution in repeat 1 of the central rod domain. Immunostaining of skeletal muscle showed weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial misfolding of the L427P mutated protein as well as a reduced refolding rate after denaturation. Based on computational homology models of the wild-type and mutated R1-2, a molecular dynamics study showed an alteration in the flexibility of the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this missense mutation hinders the dynamic properties of the entire N-terminal region of dystrophin."}

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":44,"end":54},"obj":"gene:1756"},{"id":"T1","span":{"begin":105,"end":130},"obj":"disease:C0917713"},{"id":"T2","span":{"begin":149,"end":159},"obj":"gene:1756"},{"id":"T3","span":{"begin":219,"end":244},"obj":"disease:C0917713"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes protein misfolding and mild Becker muscular dystrophy.\nMutations in the dystrophin gene without disruption of the reading frame often lead to Becker muscular dystrophy, but a genotype/phenotype correlation is difficult to establish. Amino acid substitutions may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two brothers (ages 8 and 10 years) with very mild proximal weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin gene (c.1280T\u003eC) leading to a L427P amino acid substitution in repeat 1 of the central rod domain. Immunostaining of skeletal muscle showed weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial misfolding of the L427P mutated protein as well as a reduced refolding rate after denaturation. Based on computational homology models of the wild-type and mutated R1-2, a molecular dynamics study showed an alteration in the flexibility of the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this missense mutation hinders the dynamic properties of the entire N-terminal region of dystrophin."}

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":226,"end":244},"obj":"HP_0003560"},{"id":"T2","span":{"begin":540,"end":554},"obj":"HP_0002027"},{"id":"T3","span":{"begin":550,"end":554},"obj":"HP_0012531"},{"id":"T4","span":{"begin":571,"end":601},"obj":"HP_0003236"}],"text":"Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes protein misfolding and mild Becker muscular dystrophy.\nMutations in the dystrophin gene without disruption of the reading frame often lead to Becker muscular dystrophy, but a genotype/phenotype correlation is difficult to establish. Amino acid substitutions may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two brothers (ages 8 and 10 years) with very mild proximal weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin gene (c.1280T\u003eC) leading to a L427P amino acid substitution in repeat 1 of the central rod domain. Immunostaining of skeletal muscle showed weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial misfolding of the L427P mutated protein as well as a reduced refolding rate after denaturation. Based on computational homology models of the wild-type and mutated R1-2, a molecular dynamics study showed an alteration in the flexibility of the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this missense mutation hinders the dynamic properties of the entire N-terminal region of dystrophin."}

{"project":"Allie","denotations":[{"id":"SS1_22453924_6_0","span":{"begin":1042,"end":1052},"obj":"expanded"},{"id":"SS2_22453924_6_0","span":{"begin":1054,"end":1058},"obj":"abbr"}],"relations":[{"id":"AE1_22453924_6_0","pred":"abbreviatedTo","subj":"SS1_22453924_6_0","obj":"SS2_22453924_6_0"}],"text":"Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes protein misfolding and mild Becker muscular dystrophy.\nMutations in the dystrophin gene without disruption of the reading frame often lead to Becker muscular dystrophy, but a genotype/phenotype correlation is difficult to establish. Amino acid substitutions may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two brothers (ages 8 and 10 years) with very mild proximal weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin gene (c.1280T\u003eC) leading to a L427P amino acid substitution in repeat 1 of the central rod domain. Immunostaining of skeletal muscle showed weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial misfolding of the L427P mutated protein as well as a reduced refolding rate after denaturation. Based on computational homology models of the wild-type and mutated R1-2, a molecular dynamics study showed an alteration in the flexibility of the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this missense mutation hinders the dynamic properties of the entire N-terminal region of dystrophin."}

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"22453924-0#44#54#gene1756","span":{"begin":44,"end":54},"obj":"gene1756"},{"id":"22453924-0#105#130#diseaseC0917713","span":{"begin":105,"end":130},"obj":"diseaseC0917713"}],"relations":[{"id":"44#54#gene1756105#130#diseaseC0917713","pred":"associated_with","subj":"22453924-0#44#54#gene1756","obj":"22453924-0#105#130#diseaseC0917713"}],"text":"Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes protein misfolding and mild Becker muscular dystrophy.\nMutations in the dystrophin gene without disruption of the reading frame often lead to Becker muscular dystrophy, but a genotype/phenotype correlation is difficult to establish. Amino acid substitutions may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two brothers (ages 8 and 10 years) with very mild proximal weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin gene (c.1280T\u003eC) leading to a L427P amino acid substitution in repeat 1 of the central rod domain. Immunostaining of skeletal muscle showed weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial misfolding of the L427P mutated protein as well as a reduced refolding rate after denaturation. Based on computational homology models of the wild-type and mutated R1-2, a molecular dynamics study showed an alteration in the flexibility of the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this missense mutation hinders the dynamic properties of the entire N-terminal region of dystrophin."}

{"project":"UBERON-AE","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":55,"end":62},"obj":"http://purl.obolibrary.org/obo/UBERON_0012131"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":760,"end":767},"obj":"http://purl.obolibrary.org/obo/UBERON_0012131"},{"id":"PD-UBERON-AE-B_T3","span":{"begin":580,"end":585},"obj":"http://purl.obolibrary.org/obo/UBERON_0001977"}],"text":"Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes protein misfolding and mild Becker muscular dystrophy.\nMutations in the dystrophin gene without disruption of the reading frame often lead to Becker muscular dystrophy, but a genotype/phenotype correlation is difficult to establish. Amino acid substitutions may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two brothers (ages 8 and 10 years) with very mild proximal weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin gene (c.1280T\u003eC) leading to a L427P amino acid substitution in repeat 1 of the central rod domain. Immunostaining of skeletal muscle showed weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial misfolding of the L427P mutated protein as well as a reduced refolding rate after denaturation. Based on computational homology models of the wild-type and mutated R1-2, a molecular dynamics study showed an alteration in the flexibility of the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this missense mutation hinders the dynamic properties of the entire N-terminal region of dystrophin."}

{"project":"PubCasesHPO","denotations":[{"id":"AB1","span":{"begin":226,"end":244},"obj":"HP:0003560"},{"id":"TI1","span":{"begin":112,"end":130},"obj":"HP:0003560"},{"id":"AB2","span":{"begin":540,"end":554},"obj":"HP:0002027"}],"text":"Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes protein misfolding and mild Becker muscular dystrophy.\nMutations in the dystrophin gene without disruption of the reading frame often lead to Becker muscular dystrophy, but a genotype/phenotype correlation is difficult to establish. Amino acid substitutions may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two brothers (ages 8 and 10 years) with very mild proximal weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin gene (c.1280T\u003eC) leading to a L427P amino acid substitution in repeat 1 of the central rod domain. Immunostaining of skeletal muscle showed weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial misfolding of the L427P mutated protein as well as a reduced refolding rate after denaturation. Based on computational homology models of the wild-type and mutated R1-2, a molecular dynamics study showed an alteration in the flexibility of the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this missense mutation hinders the dynamic properties of the entire N-terminal region of dystrophin."}

{"project":"performance-test","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":580,"end":585},"obj":"http://purl.obolibrary.org/obo/UBERON_0001977"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":55,"end":62},"obj":"http://purl.obolibrary.org/obo/UBERON_0012131"},{"id":"PD-UBERON-AE-B_T3","span":{"begin":760,"end":767},"obj":"http://purl.obolibrary.org/obo/UBERON_0012131"}],"text":"Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes protein misfolding and mild Becker muscular dystrophy.\nMutations in the dystrophin gene without disruption of the reading frame often lead to Becker muscular dystrophy, but a genotype/phenotype correlation is difficult to establish. Amino acid substitutions may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two brothers (ages 8 and 10 years) with very mild proximal weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin gene (c.1280T\u003eC) leading to a L427P amino acid substitution in repeat 1 of the central rod domain. Immunostaining of skeletal muscle showed weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial misfolding of the L427P mutated protein as well as a reduced refolding rate after denaturation. Based on computational homology models of the wild-type and mutated R1-2, a molecular dynamics study showed an alteration in the flexibility of the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this missense mutation hinders the dynamic properties of the entire N-terminal region of dystrophin."}

{"project":"PubCasesORDO","denotations":[{"id":"AB1","span":{"begin":219,"end":244},"obj":"ORDO:98895"},{"id":"TI1","span":{"begin":105,"end":130},"obj":"ORDO:98895"}],"namespaces":[{"prefix":"ORDO","uri":"http://www.orpha.net/ORDO/Orphanet_"}],"text":"Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes protein misfolding and mild Becker muscular dystrophy.\nMutations in the dystrophin gene without disruption of the reading frame often lead to Becker muscular dystrophy, but a genotype/phenotype correlation is difficult to establish. Amino acid substitutions may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two brothers (ages 8 and 10 years) with very mild proximal weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin gene (c.1280T\u003eC) leading to a L427P amino acid substitution in repeat 1 of the central rod domain. Immunostaining of skeletal muscle showed weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial misfolding of the L427P mutated protein as well as a reduced refolding rate after denaturation. Based on computational homology models of the wild-type and mutated R1-2, a molecular dynamics study showed an alteration in the flexibility of the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this missense mutation hinders the dynamic properties of the entire N-terminal region of dystrophin."}

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":105,"end":130},"obj":"Disease"},{"id":"T2","span":{"begin":219,"end":244},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0010311"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0010311"}],"text":"Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes protein misfolding and mild Becker muscular dystrophy.\nMutations in the dystrophin gene without disruption of the reading frame often lead to Becker muscular dystrophy, but a genotype/phenotype correlation is difficult to establish. Amino acid substitutions may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two brothers (ages 8 and 10 years) with very mild proximal weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin gene (c.1280T\u003eC) leading to a L427P amino acid substitution in repeat 1 of the central rod domain. Immunostaining of skeletal muscle showed weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial misfolding of the L427P mutated protein as well as a reduced refolding rate after denaturation. Based on computational homology models of the wild-type and mutated R1-2, a molecular dynamics study showed an alteration in the flexibility of the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this missense mutation hinders the dynamic properties of the entire N-terminal region of dystrophin."}

{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":112,"end":130},"obj":"Phenotype"},{"id":"T2","span":{"begin":226,"end":244},"obj":"Phenotype"},{"id":"T3","span":{"begin":520,"end":528},"obj":"Phenotype"},{"id":"T4","span":{"begin":540,"end":554},"obj":"Phenotype"},{"id":"T5","span":{"begin":571,"end":601},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0003560"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0003560"},{"id":"A3","pred":"hp_id","subj":"T3","obj":"HP:0025406"},{"id":"A4","pred":"hp_id","subj":"T4","obj":"HP:0002027"},{"id":"A5","pred":"hp_id","subj":"T5","obj":"HP:0003236"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}],"text":"Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes protein misfolding and mild Becker muscular dystrophy.\nMutations in the dystrophin gene without disruption of the reading frame often lead to Becker muscular dystrophy, but a genotype/phenotype correlation is difficult to establish. Amino acid substitutions may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two brothers (ages 8 and 10 years) with very mild proximal weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin gene (c.1280T\u003eC) leading to a L427P amino acid substitution in repeat 1 of the central rod domain. Immunostaining of skeletal muscle showed weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial misfolding of the L427P mutated protein as well as a reduced refolding rate after denaturation. Based on computational homology models of the wild-type and mutated R1-2, a molecular dynamics study showed an alteration in the flexibility of the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this missense mutation hinders the dynamic properties of the entire N-terminal region of dystrophin."}

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":768,"end":771},"obj":"Body_part"},{"id":"T2","span":{"begin":798,"end":813},"obj":"Body_part"},{"id":"T5","span":{"begin":1379,"end":1384},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL_0000604"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0001134"},{"id":"A3","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0014892"},{"id":"A4","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0014895"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_0000464"}],"text":"Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes protein misfolding and mild Becker muscular dystrophy.\nMutations in the dystrophin gene without disruption of the reading frame often lead to Becker muscular dystrophy, but a genotype/phenotype correlation is difficult to establish. Amino acid substitutions may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two brothers (ages 8 and 10 years) with very mild proximal weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin gene (c.1280T\u003eC) leading to a L427P amino acid substitution in repeat 1 of the central rod domain. Immunostaining of skeletal muscle showed weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial misfolding of the L427P mutated protein as well as a reduced refolding rate after denaturation. Based on computational homology models of the wild-type and mutated R1-2, a molecular dynamics study showed an alteration in the flexibility of the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this missense mutation hinders the dynamic properties of the entire N-terminal region of dystrophin."}

{"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":511,"end":519},"obj":"Body_part"},{"id":"T2","span":{"begin":798,"end":813},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000491"},{"id":"A2","pred":"mat_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MAT_0000302"}],"text":"Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes protein misfolding and mild Becker muscular dystrophy.\nMutations in the dystrophin gene without disruption of the reading frame often lead to Becker muscular dystrophy, but a genotype/phenotype correlation is difficult to establish. Amino acid substitutions may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two brothers (ages 8 and 10 years) with very mild proximal weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin gene (c.1280T\u003eC) leading to a L427P amino acid substitution in repeat 1 of the central rod domain. Immunostaining of skeletal muscle showed weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial misfolding of the L427P mutated protein as well as a reduced refolding rate after denaturation. Based on computational homology models of the wild-type and mutated R1-2, a molecular dynamics study showed an alteration in the flexibility of the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this missense mutation hinders the dynamic properties of the entire N-terminal region of dystrophin."}