Genotype-phenotype correlation in five Pelizaeus-Merzbacher disease patients with PLP1 gene duplications
Pelizaeus–Merzbacher disease (PMD) is an X‐linked myelination disorder most frequently caused by duplication of a genomic segment of variable length containing the PLP1 gene. We studied five PMD male patients affected by the classic PMD form carrying a PLP1 gene duplication. On the basis of clinical...
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| Veröffentlicht in: | Clinical genetics 2008-03, Vol.73 (3), p.279-287 |
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| creator | Regis, S Biancheri, R Bertini, E Burlina, A Lualdi, S Bianco, MG Devescovi, R Rossi, A Uziel, G Filocamo, M |
| description | Pelizaeus–Merzbacher disease (PMD) is an X‐linked myelination disorder most frequently caused by duplication of a genomic segment of variable length containing the PLP1 gene. We studied five PMD male patients affected by the classic PMD form carrying a PLP1 gene duplication. On the basis of clinical and neuroradiological features, two of the five patients appeared to be the most severely affected. In order to establish a possible genotype–phenotype correlation, the extent of the duplication was determined in each patient and in the respective mother by quantifying the copy number of genomic markers surrounding the PLP1 gene by a real‐time PCR‐based approach. Duplications, ranging in size from 167–195 to 580–700 kb, were in the same genomic interval of the majority of the reported duplications. The extent of the duplicated genomic segments does not correlate with the clinical severity. Interestingly enough, each duplication had one of the two breakpoints in or near to low copy repeats (LCRs), supporting recent evidence concerning a possible role of LCRs in the generation of the duplications in PMD. |
| doi_str_mv | 10.1111/j.1399-0004.2007.00961.x |
| format | Article |
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We studied five PMD male patients affected by the classic PMD form carrying a PLP1 gene duplication. On the basis of clinical and neuroradiological features, two of the five patients appeared to be the most severely affected. In order to establish a possible genotype–phenotype correlation, the extent of the duplication was determined in each patient and in the respective mother by quantifying the copy number of genomic markers surrounding the PLP1 gene by a real‐time PCR‐based approach. Duplications, ranging in size from 167–195 to 580–700 kb, were in the same genomic interval of the majority of the reported duplications. The extent of the duplicated genomic segments does not correlate with the clinical severity. Interestingly enough, each duplication had one of the two breakpoints in or near to low copy repeats (LCRs), supporting recent evidence concerning a possible role of LCRs in the generation of the duplications in PMD.</description><identifier>ISSN: 0009-9163</identifier><identifier>EISSN: 1399-0004</identifier><identifier>DOI: 10.1111/j.1399-0004.2007.00961.x</identifier><identifier>PMID: 18190592</identifier><identifier>CODEN: CLGNAY</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Biological and medical sciences ; Child ; Child, Preschool ; Correlation analysis ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Fundamental and applied biological sciences. Psychology ; Gene Dosage ; Gene Duplication ; General aspects. Genetic counseling ; Genetic disorders ; Genetic markers ; Genetics of eukaryotes. Biological and molecular evolution ; Genomics ; Genotype ; Genotype & phenotype ; Humans ; Infant ; Infant, Newborn ; low copy repeats ; Magnetic Resonance Imaging ; Male ; Medical genetics ; Medical sciences ; Membrane Proteins - genetics ; Molecular and cellular biology ; Myelin Proteolipid Protein - genetics ; Neurology ; Pelizaeus-Merzbacher disease ; Pelizaeus-Merzbacher Disease - genetics ; Phenotype ; PLP1 ; real-time PCR</subject><ispartof>Clinical genetics, 2008-03, Vol.73 (3), p.279-287</ispartof><rights>2008 The Authors Journal compilation</rights><rights>2008 INIST-CNRS</rights><rights>2008 Blackwell Munksgaard</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4611-57be650b14cdeac37c18c76156bf54bc6fe8877a64264a07000e22bcc6c793313</citedby><cites>FETCH-LOGICAL-c4611-57be650b14cdeac37c18c76156bf54bc6fe8877a64264a07000e22bcc6c793313</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1399-0004.2007.00961.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1399-0004.2007.00961.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27922,27923,45572,45573</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20141189$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18190592$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Regis, S</creatorcontrib><creatorcontrib>Biancheri, R</creatorcontrib><creatorcontrib>Bertini, E</creatorcontrib><creatorcontrib>Burlina, A</creatorcontrib><creatorcontrib>Lualdi, S</creatorcontrib><creatorcontrib>Bianco, MG</creatorcontrib><creatorcontrib>Devescovi, R</creatorcontrib><creatorcontrib>Rossi, A</creatorcontrib><creatorcontrib>Uziel, G</creatorcontrib><creatorcontrib>Filocamo, M</creatorcontrib><title>Genotype-phenotype correlation in five Pelizaeus-Merzbacher disease patients with PLP1 gene duplications</title><title>Clinical genetics</title><addtitle>Clin Genet</addtitle><description>Pelizaeus–Merzbacher disease (PMD) is an X‐linked myelination disorder most frequently caused by duplication of a genomic segment of variable length containing the PLP1 gene. We studied five PMD male patients affected by the classic PMD form carrying a PLP1 gene duplication. On the basis of clinical and neuroradiological features, two of the five patients appeared to be the most severely affected. In order to establish a possible genotype–phenotype correlation, the extent of the duplication was determined in each patient and in the respective mother by quantifying the copy number of genomic markers surrounding the PLP1 gene by a real‐time PCR‐based approach. Duplications, ranging in size from 167–195 to 580–700 kb, were in the same genomic interval of the majority of the reported duplications. The extent of the duplicated genomic segments does not correlate with the clinical severity. Interestingly enough, each duplication had one of the two breakpoints in or near to low copy repeats (LCRs), supporting recent evidence concerning a possible role of LCRs in the generation of the duplications in PMD.</description><subject>Biological and medical sciences</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Correlation analysis</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Dosage</subject><subject>Gene Duplication</subject><subject>General aspects. Genetic counseling</subject><subject>Genetic disorders</subject><subject>Genetic markers</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Genomics</subject><subject>Genotype</subject><subject>Genotype & phenotype</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>low copy repeats</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Medical genetics</subject><subject>Medical sciences</subject><subject>Membrane Proteins - genetics</subject><subject>Molecular and cellular biology</subject><subject>Myelin Proteolipid Protein - genetics</subject><subject>Neurology</subject><subject>Pelizaeus-Merzbacher disease</subject><subject>Pelizaeus-Merzbacher Disease - genetics</subject><subject>Phenotype</subject><subject>PLP1</subject><subject>real-time PCR</subject><issn>0009-9163</issn><issn>1399-0004</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUFv0zAUxy0EYmXwFZCFxDHBL07sWOKCqlGmFegBmMTFctwX6pIlmZ2wdp8et43KFV-eLf9-z_bfhFBgKcTxbpsCVyphjOVpxphMGVMC0t0TMjtvPCWzWFSiQPAL8iKEbVxyWajn5AJKUKxQ2YxsFth2w77HpN9MM2o777Exg-ta6lpauz9IV9i4R4NjSD6jf6yM3aCnaxfQBKR9ZLEdAn1ww4auliugv7BFuh77xtljo_CSPKtNE_DVVC_J949X3-afkuXXxfX8wzKxuQBIClmhKFgFuV2jsVxaKK0UUIiqLvLKihrLUkoj8kzkhsn4JsyyylphpeIc-CV5c-rb--5-xDDobTf6Nh6pD0kVUSgiVJ4g67sQPNa69-7O-L0Gpg8J660-BKkPQR49fUxY76L6euo_Vne4_idOkUbg7QSYYE1Te9NaF85cxiAHKFXk3p-4B9fg_r8voOeLqziJenLSXRhwd9aN_62FjN-sb78stLhZ8dufP-aa8b-_dqYR</recordid><startdate>200803</startdate><enddate>200803</enddate><creator>Regis, S</creator><creator>Biancheri, R</creator><creator>Bertini, E</creator><creator>Burlina, A</creator><creator>Lualdi, S</creator><creator>Bianco, MG</creator><creator>Devescovi, R</creator><creator>Rossi, A</creator><creator>Uziel, G</creator><creator>Filocamo, M</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><scope>BSCLL</scope><scope>IQODW</scope><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>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>200803</creationdate><title>Genotype-phenotype correlation in five Pelizaeus-Merzbacher disease patients with PLP1 gene duplications</title><author>Regis, S ; Biancheri, R ; Bertini, E ; Burlina, A ; Lualdi, S ; Bianco, MG ; Devescovi, R ; Rossi, A ; Uziel, G ; Filocamo, M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4611-57be650b14cdeac37c18c76156bf54bc6fe8877a64264a07000e22bcc6c793313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Biological and medical sciences</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Correlation analysis</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Dosage</topic><topic>Gene Duplication</topic><topic>General aspects. Genetic counseling</topic><topic>Genetic disorders</topic><topic>Genetic markers</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Genomics</topic><topic>Genotype</topic><topic>Genotype & phenotype</topic><topic>Humans</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>low copy repeats</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Medical genetics</topic><topic>Medical sciences</topic><topic>Membrane Proteins - genetics</topic><topic>Molecular and cellular biology</topic><topic>Myelin Proteolipid Protein - genetics</topic><topic>Neurology</topic><topic>Pelizaeus-Merzbacher disease</topic><topic>Pelizaeus-Merzbacher Disease - genetics</topic><topic>Phenotype</topic><topic>PLP1</topic><topic>real-time PCR</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Regis, S</creatorcontrib><creatorcontrib>Biancheri, R</creatorcontrib><creatorcontrib>Bertini, E</creatorcontrib><creatorcontrib>Burlina, A</creatorcontrib><creatorcontrib>Lualdi, S</creatorcontrib><creatorcontrib>Bianco, MG</creatorcontrib><creatorcontrib>Devescovi, R</creatorcontrib><creatorcontrib>Rossi, A</creatorcontrib><creatorcontrib>Uziel, G</creatorcontrib><creatorcontrib>Filocamo, M</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</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>Clinical genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Regis, S</au><au>Biancheri, R</au><au>Bertini, E</au><au>Burlina, A</au><au>Lualdi, S</au><au>Bianco, MG</au><au>Devescovi, R</au><au>Rossi, A</au><au>Uziel, G</au><au>Filocamo, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genotype-phenotype correlation in five Pelizaeus-Merzbacher disease patients with PLP1 gene duplications</atitle><jtitle>Clinical genetics</jtitle><addtitle>Clin Genet</addtitle><date>2008-03</date><risdate>2008</risdate><volume>73</volume><issue>3</issue><spage>279</spage><epage>287</epage><pages>279-287</pages><issn>0009-9163</issn><eissn>1399-0004</eissn><coden>CLGNAY</coden><abstract>Pelizaeus–Merzbacher disease (PMD) is an X‐linked myelination disorder most frequently caused by duplication of a genomic segment of variable length containing the PLP1 gene. We studied five PMD male patients affected by the classic PMD form carrying a PLP1 gene duplication. On the basis of clinical and neuroradiological features, two of the five patients appeared to be the most severely affected. In order to establish a possible genotype–phenotype correlation, the extent of the duplication was determined in each patient and in the respective mother by quantifying the copy number of genomic markers surrounding the PLP1 gene by a real‐time PCR‐based approach. Duplications, ranging in size from 167–195 to 580–700 kb, were in the same genomic interval of the majority of the reported duplications. The extent of the duplicated genomic segments does not correlate with the clinical severity. Interestingly enough, each duplication had one of the two breakpoints in or near to low copy repeats (LCRs), supporting recent evidence concerning a possible role of LCRs in the generation of the duplications in PMD.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>18190592</pmid><doi>10.1111/j.1399-0004.2007.00961.x</doi><tpages>9</tpages></addata></record> |
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| ispartof | Clinical genetics, 2008-03, Vol.73 (3), p.279-287 |
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| subjects | Biological and medical sciences Child Child, Preschool Correlation analysis Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Fundamental and applied biological sciences. Psychology Gene Dosage Gene Duplication General aspects. Genetic counseling Genetic disorders Genetic markers Genetics of eukaryotes. Biological and molecular evolution Genomics Genotype Genotype & phenotype Humans Infant Infant, Newborn low copy repeats Magnetic Resonance Imaging Male Medical genetics Medical sciences Membrane Proteins - genetics Molecular and cellular biology Myelin Proteolipid Protein - genetics Neurology Pelizaeus-Merzbacher disease Pelizaeus-Merzbacher Disease - genetics Phenotype PLP1 real-time PCR |
| title | Genotype-phenotype correlation in five Pelizaeus-Merzbacher disease patients with PLP1 gene duplications |
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