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The medical genetics of dystrophinopathies: Molecular genetic diagnosis and its impact on clinical practice
Abstract A large variety of mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophies, diseases affecting predominantly the striated muscles (skeletal and cardiac). Rare mutations also account for the allelic disorder isolated X-linked dilated cardiomyopathy. Dystrophin protein...
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Published in: | Neuromuscular disorders : NMD 2013-01, Vol.23 (1), p.4-14 |
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description | Abstract A large variety of mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophies, diseases affecting predominantly the striated muscles (skeletal and cardiac). Rare mutations also account for the allelic disorder isolated X-linked dilated cardiomyopathy. Dystrophin protein is encoded by a huge gene located on the X chromosome and the understanding of its complex genomic architecture has unraveled general key functions in gene expression regulation. Dystrophin also exists as a number of other tissue specific isoforms, some exclusively or predominantly expressed in the brain and/or in other tissues. Genotype definition of the dystrophin gene in patients with dystrophinopathies has taught us much about functionally important domains of the protein itself and has also provided insights regarding several regulatory mechanisms governing the gene expression profile. This review focuses on the current understanding of the dystrophin mutations heterogeneity, genotype-phenotype correlations, as well as interpretation of the functional significance of mutations that often require non routine genetic studies. It also explores the impact of genetic diagnosis on clinical definition and on the discovery of biomarkers and personalized therapies. Our aim is to offer an overview of the medical genetic approach on the dystrophin gene and dystrophinopathies with implications for clinical practice and therapeutic perspectives. |
doi_str_mv | 10.1016/j.nmd.2012.09.002 |
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Rare mutations also account for the allelic disorder isolated X-linked dilated cardiomyopathy. Dystrophin protein is encoded by a huge gene located on the X chromosome and the understanding of its complex genomic architecture has unraveled general key functions in gene expression regulation. Dystrophin also exists as a number of other tissue specific isoforms, some exclusively or predominantly expressed in the brain and/or in other tissues. Genotype definition of the dystrophin gene in patients with dystrophinopathies has taught us much about functionally important domains of the protein itself and has also provided insights regarding several regulatory mechanisms governing the gene expression profile. This review focuses on the current understanding of the dystrophin mutations heterogeneity, genotype-phenotype correlations, as well as interpretation of the functional significance of mutations that often require non routine genetic studies. It also explores the impact of genetic diagnosis on clinical definition and on the discovery of biomarkers and personalized therapies. Our aim is to offer an overview of the medical genetic approach on the dystrophin gene and dystrophinopathies with implications for clinical practice and therapeutic perspectives.</description><identifier>ISSN: 0960-8966</identifier><identifier>EISSN: 1873-2364</identifier><identifier>DOI: 10.1016/j.nmd.2012.09.002</identifier><identifier>PMID: 23116935</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>Duchenne and Becker muscular dystrophies ; Dystrophin ; Dystrophin - genetics ; Female ; Genetic Testing - methods ; Genotype ; Genotype phenotype correlation ; Humans ; Male ; Molecular Biology - methods ; Molecular genetics ; Muscular Dystrophies - diagnosis ; Muscular Dystrophies - genetics ; Mutation - genetics ; Mutations ; Neurology ; Pedigree ; Phenotype ; Practice Patterns, Physicians' - trends</subject><ispartof>Neuromuscular disorders : NMD, 2013-01, Vol.23 (1), p.4-14</ispartof><rights>Elsevier B.V.</rights><rights>2012 Elsevier B.V.</rights><rights>Copyright © 2012 Elsevier B.V. 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Rare mutations also account for the allelic disorder isolated X-linked dilated cardiomyopathy. Dystrophin protein is encoded by a huge gene located on the X chromosome and the understanding of its complex genomic architecture has unraveled general key functions in gene expression regulation. Dystrophin also exists as a number of other tissue specific isoforms, some exclusively or predominantly expressed in the brain and/or in other tissues. Genotype definition of the dystrophin gene in patients with dystrophinopathies has taught us much about functionally important domains of the protein itself and has also provided insights regarding several regulatory mechanisms governing the gene expression profile. This review focuses on the current understanding of the dystrophin mutations heterogeneity, genotype-phenotype correlations, as well as interpretation of the functional significance of mutations that often require non routine genetic studies. It also explores the impact of genetic diagnosis on clinical definition and on the discovery of biomarkers and personalized therapies. Our aim is to offer an overview of the medical genetic approach on the dystrophin gene and dystrophinopathies with implications for clinical practice and therapeutic perspectives.</description><subject>Duchenne and Becker muscular dystrophies</subject><subject>Dystrophin</subject><subject>Dystrophin - genetics</subject><subject>Female</subject><subject>Genetic Testing - methods</subject><subject>Genotype</subject><subject>Genotype phenotype correlation</subject><subject>Humans</subject><subject>Male</subject><subject>Molecular Biology - methods</subject><subject>Molecular genetics</subject><subject>Muscular Dystrophies - diagnosis</subject><subject>Muscular Dystrophies - genetics</subject><subject>Mutation - genetics</subject><subject>Mutations</subject><subject>Neurology</subject><subject>Pedigree</subject><subject>Phenotype</subject><subject>Practice Patterns, Physicians' - trends</subject><issn>0960-8966</issn><issn>1873-2364</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqNkj-P1DAUxC0E4paDD0CDXNIkPDuJHYOEhE78kw5RcNSWY7_cei9rBztB2m-Pl72loEBUT3r6zRQzQ8hzBjUDJl7t6rB3NQfGa1A1AH9ANqyXTcUb0T4kG1ACql4JcUGe5LwDYJ0U8jG54A1jQjXdhtzdbJHu0XlrJnqLARdvM40jdYe8pDhvfYizWbYe82v6JU5o18mkM0mdN7chZp-pCY76JVO_n41daAzUTj78tp1T-XiLT8mj0UwZn93fS_L9w_ubq0_V9dePn6_eXVe262CpLKJENai-UQKhddiO6JTi4HoFnCnH5QgOxKgGUD0b-kH2Q9-VI21rnGsuycuT75zijxXzovc-W5wmEzCuWTPedww4l_AfqGy6tlGtLCg7oTbFnBOOek5-b9JBM9DHOvROlzr0sQ4NSpc6iubFvf06lJD_KM75F-DNCcCSx0-PSWfrMdhSSEK7aBf9P-3f_qU-Z36HB8y7uKZQgtZM56LR3457OM6BcQBR1tD8Ahs0sJM</recordid><startdate>20130101</startdate><enddate>20130101</enddate><creator>Ferlini, Alessandra</creator><creator>Neri, Marcella</creator><creator>Gualandi, Francesca</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20130101</creationdate><title>The medical genetics of dystrophinopathies: Molecular genetic diagnosis and its impact on clinical practice</title><author>Ferlini, Alessandra ; Neri, Marcella ; Gualandi, Francesca</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c550t-cee7e9b98396e04de4fed9920d890219d27f0d06f9b0981b8b78b858b77c4add3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Duchenne and Becker muscular dystrophies</topic><topic>Dystrophin</topic><topic>Dystrophin - genetics</topic><topic>Female</topic><topic>Genetic Testing - methods</topic><topic>Genotype</topic><topic>Genotype phenotype correlation</topic><topic>Humans</topic><topic>Male</topic><topic>Molecular Biology - methods</topic><topic>Molecular genetics</topic><topic>Muscular Dystrophies - diagnosis</topic><topic>Muscular Dystrophies - genetics</topic><topic>Mutation - genetics</topic><topic>Mutations</topic><topic>Neurology</topic><topic>Pedigree</topic><topic>Phenotype</topic><topic>Practice Patterns, Physicians' - trends</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ferlini, Alessandra</creatorcontrib><creatorcontrib>Neri, Marcella</creatorcontrib><creatorcontrib>Gualandi, Francesca</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Neuromuscular disorders : NMD</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ferlini, Alessandra</au><au>Neri, Marcella</au><au>Gualandi, Francesca</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The medical genetics of dystrophinopathies: Molecular genetic diagnosis and its impact on clinical practice</atitle><jtitle>Neuromuscular disorders : NMD</jtitle><addtitle>Neuromuscul Disord</addtitle><date>2013-01-01</date><risdate>2013</risdate><volume>23</volume><issue>1</issue><spage>4</spage><epage>14</epage><pages>4-14</pages><issn>0960-8966</issn><eissn>1873-2364</eissn><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-3</notes><notes>content type line 23</notes><notes>ObjectType-Review-1</notes><notes>ObjectType-Feature-1</notes><abstract>Abstract A large variety of mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophies, diseases affecting predominantly the striated muscles (skeletal and cardiac). Rare mutations also account for the allelic disorder isolated X-linked dilated cardiomyopathy. Dystrophin protein is encoded by a huge gene located on the X chromosome and the understanding of its complex genomic architecture has unraveled general key functions in gene expression regulation. Dystrophin also exists as a number of other tissue specific isoforms, some exclusively or predominantly expressed in the brain and/or in other tissues. Genotype definition of the dystrophin gene in patients with dystrophinopathies has taught us much about functionally important domains of the protein itself and has also provided insights regarding several regulatory mechanisms governing the gene expression profile. This review focuses on the current understanding of the dystrophin mutations heterogeneity, genotype-phenotype correlations, as well as interpretation of the functional significance of mutations that often require non routine genetic studies. It also explores the impact of genetic diagnosis on clinical definition and on the discovery of biomarkers and personalized therapies. Our aim is to offer an overview of the medical genetic approach on the dystrophin gene and dystrophinopathies with implications for clinical practice and therapeutic perspectives.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>23116935</pmid><doi>10.1016/j.nmd.2012.09.002</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Duchenne and Becker muscular dystrophies Dystrophin Dystrophin - genetics Female Genetic Testing - methods Genotype Genotype phenotype correlation Humans Male Molecular Biology - methods Molecular genetics Muscular Dystrophies - diagnosis Muscular Dystrophies - genetics Mutation - genetics Mutations Neurology Pedigree Phenotype Practice Patterns, Physicians' - trends |
title | The medical genetics of dystrophinopathies: Molecular genetic diagnosis and its impact on clinical practice |
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