Mitochondrial DNA defects in Brazilian patients with chronic progressive external ophthalmoplegia
We report herein on eleven Brazilian patients with mitochondrial DNA (mtDNA) deletions, found among thirteen patients with chronic progressive external ophthalmoplegia (CPEO) and ragged-red fibers (RRF). The molecular data was correlated with the morphological and clinical findings. The muscle biops...
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Veröffentlicht in: | Journal of the neurological sciences 1997-11, Vol.152 (2), p.160-165 |
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description | We report herein on eleven Brazilian patients with mitochondrial DNA (mtDNA) deletions, found among thirteen patients with chronic progressive external ophthalmoplegia (CPEO) and ragged-red fibers (RRF). The molecular data was correlated with the morphological and clinical findings. The muscle biopsies were studied by histochemistry, immunohistochemistry and DNA analysis. Muscle mtDNA deletions were mapped and quantitated by Southern blot analysis, polymerase chain reaction and sequencing. Of the eleven patients, ten had CPEO without multisystemic involvement and one had Kearns-Sayre syndrome. Three patients had multiple deletions, two of them with no apparent family history. Eight patients showed heteroplasmic single deletions, ranging in length from 2309 to 7566 bp; three of them had the same `common deletion' of 4977 bp. The proportion of deleted mtDNA ranged from 14 to 89%. Immunohistochemical studies revealed decreased reactivity with the mtDNA-encoded subunit II of cytochrome
c oxidase (COX) in all patients, but preserved activity with the nuclear-encoded COX subunit IV in COX-deficient fibers. Two cases presented a few COX-negative fibers with reduced COX IV immunostaining. We found a high frequency of mtDNA deletions in Brazilian patients with CPEO. There was no correlation between clinical severity, morphological findings and the size or amount of the mutated mtDNA in muscle, suggesting that there are still unknown factors influencing the disease phenotype. |
doi_str_mv | 10.1016/S0022-510X(97)00158-5 |
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c oxidase (COX) in all patients, but preserved activity with the nuclear-encoded COX subunit IV in COX-deficient fibers. Two cases presented a few COX-negative fibers with reduced COX IV immunostaining. We found a high frequency of mtDNA deletions in Brazilian patients with CPEO. There was no correlation between clinical severity, morphological findings and the size or amount of the mutated mtDNA in muscle, suggesting that there are still unknown factors influencing the disease phenotype.</description><identifier>ISSN: 0022-510X</identifier><identifier>EISSN: 1878-5883</identifier><identifier>DOI: 10.1016/S0022-510X(97)00158-5</identifier><identifier>PMID: 9415537</identifier><identifier>CODEN: JNSCAG</identifier><language>eng</language><publisher>Shannon: Elsevier B.V</publisher><subject>Adolescent ; Adult ; Base Sequence ; Biological and medical sciences ; Biopsy ; Brazil ; Child ; Diseases of visual field, optic nerve, optic chiasma and optic tracts ; DNA, Mitochondrial - genetics ; Female ; Humans ; Kearns-Sayre syndrome ; Kearns-Sayre Syndrome - genetics ; Kearns-Sayre Syndrome - pathology ; Kearns-Sayre Syndrome - physiopathology ; Male ; Medical sciences ; Middle Aged ; Mitochondrial DNA ; Mitochondrial myopathy ; Molecular Sequence Data ; Muscle Fibers, Fast-Twitch - pathology ; Muscle Fibers, Skeletal - pathology ; Muscle, Skeletal - metabolism ; Muscle, Skeletal - pathology ; Ophthalmology ; Ophthalmoplegia ; Ophthalmoplegia, Chronic Progressive External - genetics ; Ophthalmoplegia, Chronic Progressive External - pathology ; Ophthalmoplegia, Chronic Progressive External - physiopathology ; Polymerase Chain Reaction ; Sequence Deletion</subject><ispartof>Journal of the neurological sciences, 1997-11, Vol.152 (2), p.160-165</ispartof><rights>1997 Elsevier Science B.V.</rights><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-512ea9cccf1adab7a211c86ecf3887bef24a450dc2935563ba3f85f5c0ab212b3</citedby><cites>FETCH-LOGICAL-c467t-512ea9cccf1adab7a211c86ecf3887bef24a450dc2935563ba3f85f5c0ab212b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0022-510X(97)00158-5$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2057061$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9415537$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kiyomoto, B.H</creatorcontrib><creatorcontrib>Tengan, C.H</creatorcontrib><creatorcontrib>Moraes, C.T</creatorcontrib><creatorcontrib>Oliveira, A.S.B</creatorcontrib><creatorcontrib>Gabbai, A.A</creatorcontrib><title>Mitochondrial DNA defects in Brazilian patients with chronic progressive external ophthalmoplegia</title><title>Journal of the neurological sciences</title><addtitle>J Neurol Sci</addtitle><description>We report herein on eleven Brazilian patients with mitochondrial DNA (mtDNA) deletions, found among thirteen patients with chronic progressive external ophthalmoplegia (CPEO) and ragged-red fibers (RRF). The molecular data was correlated with the morphological and clinical findings. The muscle biopsies were studied by histochemistry, immunohistochemistry and DNA analysis. Muscle mtDNA deletions were mapped and quantitated by Southern blot analysis, polymerase chain reaction and sequencing. Of the eleven patients, ten had CPEO without multisystemic involvement and one had Kearns-Sayre syndrome. Three patients had multiple deletions, two of them with no apparent family history. Eight patients showed heteroplasmic single deletions, ranging in length from 2309 to 7566 bp; three of them had the same `common deletion' of 4977 bp. The proportion of deleted mtDNA ranged from 14 to 89%. Immunohistochemical studies revealed decreased reactivity with the mtDNA-encoded subunit II of cytochrome
c oxidase (COX) in all patients, but preserved activity with the nuclear-encoded COX subunit IV in COX-deficient fibers. Two cases presented a few COX-negative fibers with reduced COX IV immunostaining. We found a high frequency of mtDNA deletions in Brazilian patients with CPEO. There was no correlation between clinical severity, morphological findings and the size or amount of the mutated mtDNA in muscle, suggesting that there are still unknown factors influencing the disease phenotype.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>Brazil</subject><subject>Child</subject><subject>Diseases of visual field, optic nerve, optic chiasma and optic tracts</subject><subject>DNA, Mitochondrial - genetics</subject><subject>Female</subject><subject>Humans</subject><subject>Kearns-Sayre syndrome</subject><subject>Kearns-Sayre Syndrome - genetics</subject><subject>Kearns-Sayre Syndrome - pathology</subject><subject>Kearns-Sayre Syndrome - physiopathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Mitochondrial DNA</subject><subject>Mitochondrial myopathy</subject><subject>Molecular Sequence Data</subject><subject>Muscle Fibers, Fast-Twitch - pathology</subject><subject>Muscle Fibers, Skeletal - pathology</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscle, Skeletal - pathology</subject><subject>Ophthalmology</subject><subject>Ophthalmoplegia</subject><subject>Ophthalmoplegia, Chronic Progressive External - genetics</subject><subject>Ophthalmoplegia, Chronic Progressive External - pathology</subject><subject>Ophthalmoplegia, Chronic Progressive External - physiopathology</subject><subject>Polymerase Chain Reaction</subject><subject>Sequence Deletion</subject><issn>0022-510X</issn><issn>1878-5883</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi0EKtvCT6iUA0JwWLDjOLZPqJTyIRU4ABI3azIZN0bZOLWz5ePX43ZXe-1prJlnxq_el7FTwV8JLtrX3ziv67US_OcLq19yLpRZqwdsJYwuD2PkQ7Y6II_Zcc6_OOetMfaIHdlGKCX1isHnsEQc4tSnAGP17stZ1ZMnXHIVpuptgn9hDDBVMyyBptL9HZahwiHFKWA1p3iVKOdwQxX9WShN5Uach2WAcRPnka4CPGGPPIyZnu7rCfvx_uL7-cf15dcPn87PLtfYtHopKmsCi4heQA-dhloINC2hl8bojnzdQKN4j7WVSrWyA-mN8go5dLWoO3nCnu_uFlHXW8qL24SMNI4wUdxmp21jLFfNvaBopW2kNAVUOxBTzDmRd3MKG0h_neDuNgN3l4G7NdhZ7e4ycKrsne4_2HYb6g9be9PL_Nl-Dhlh9AkmDPmA1Vxp3oqCvdlhVFy7CZRcxpIBUh9SCcj1Mdwj5D8r8KVf</recordid><startdate>19971125</startdate><enddate>19971125</enddate><creator>Kiyomoto, B.H</creator><creator>Tengan, C.H</creator><creator>Moraes, C.T</creator><creator>Oliveira, A.S.B</creator><creator>Gabbai, A.A</creator><general>Elsevier B.V</general><general>Elsevier Science</general><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>7X8</scope></search><sort><creationdate>19971125</creationdate><title>Mitochondrial DNA defects in Brazilian patients with chronic progressive external ophthalmoplegia</title><author>Kiyomoto, B.H ; Tengan, C.H ; Moraes, C.T ; Oliveira, A.S.B ; Gabbai, A.A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-512ea9cccf1adab7a211c86ecf3887bef24a450dc2935563ba3f85f5c0ab212b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Biopsy</topic><topic>Brazil</topic><topic>Child</topic><topic>Diseases of visual field, optic nerve, optic chiasma and optic tracts</topic><topic>DNA, Mitochondrial - genetics</topic><topic>Female</topic><topic>Humans</topic><topic>Kearns-Sayre syndrome</topic><topic>Kearns-Sayre Syndrome - genetics</topic><topic>Kearns-Sayre Syndrome - pathology</topic><topic>Kearns-Sayre Syndrome - physiopathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Mitochondrial DNA</topic><topic>Mitochondrial myopathy</topic><topic>Molecular Sequence Data</topic><topic>Muscle Fibers, Fast-Twitch - pathology</topic><topic>Muscle Fibers, Skeletal - pathology</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscle, Skeletal - pathology</topic><topic>Ophthalmology</topic><topic>Ophthalmoplegia</topic><topic>Ophthalmoplegia, Chronic Progressive External - genetics</topic><topic>Ophthalmoplegia, Chronic Progressive External - pathology</topic><topic>Ophthalmoplegia, Chronic Progressive External - physiopathology</topic><topic>Polymerase Chain Reaction</topic><topic>Sequence Deletion</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kiyomoto, B.H</creatorcontrib><creatorcontrib>Tengan, C.H</creatorcontrib><creatorcontrib>Moraes, C.T</creatorcontrib><creatorcontrib>Oliveira, A.S.B</creatorcontrib><creatorcontrib>Gabbai, A.A</creatorcontrib><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>MEDLINE - Academic</collection><jtitle>Journal of the neurological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kiyomoto, B.H</au><au>Tengan, C.H</au><au>Moraes, C.T</au><au>Oliveira, A.S.B</au><au>Gabbai, A.A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mitochondrial DNA defects in Brazilian patients with chronic progressive external ophthalmoplegia</atitle><jtitle>Journal of the neurological sciences</jtitle><addtitle>J Neurol Sci</addtitle><date>1997-11-25</date><risdate>1997</risdate><volume>152</volume><issue>2</issue><spage>160</spage><epage>165</epage><pages>160-165</pages><issn>0022-510X</issn><eissn>1878-5883</eissn><coden>JNSCAG</coden><abstract>We report herein on eleven Brazilian patients with mitochondrial DNA (mtDNA) deletions, found among thirteen patients with chronic progressive external ophthalmoplegia (CPEO) and ragged-red fibers (RRF). The molecular data was correlated with the morphological and clinical findings. The muscle biopsies were studied by histochemistry, immunohistochemistry and DNA analysis. Muscle mtDNA deletions were mapped and quantitated by Southern blot analysis, polymerase chain reaction and sequencing. Of the eleven patients, ten had CPEO without multisystemic involvement and one had Kearns-Sayre syndrome. Three patients had multiple deletions, two of them with no apparent family history. Eight patients showed heteroplasmic single deletions, ranging in length from 2309 to 7566 bp; three of them had the same `common deletion' of 4977 bp. The proportion of deleted mtDNA ranged from 14 to 89%. Immunohistochemical studies revealed decreased reactivity with the mtDNA-encoded subunit II of cytochrome
c oxidase (COX) in all patients, but preserved activity with the nuclear-encoded COX subunit IV in COX-deficient fibers. Two cases presented a few COX-negative fibers with reduced COX IV immunostaining. We found a high frequency of mtDNA deletions in Brazilian patients with CPEO. There was no correlation between clinical severity, morphological findings and the size or amount of the mutated mtDNA in muscle, suggesting that there are still unknown factors influencing the disease phenotype.</abstract><cop>Shannon</cop><pub>Elsevier B.V</pub><pmid>9415537</pmid><doi>10.1016/S0022-510X(97)00158-5</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adolescent Adult Base Sequence Biological and medical sciences Biopsy Brazil Child Diseases of visual field, optic nerve, optic chiasma and optic tracts DNA, Mitochondrial - genetics Female Humans Kearns-Sayre syndrome Kearns-Sayre Syndrome - genetics Kearns-Sayre Syndrome - pathology Kearns-Sayre Syndrome - physiopathology Male Medical sciences Middle Aged Mitochondrial DNA Mitochondrial myopathy Molecular Sequence Data Muscle Fibers, Fast-Twitch - pathology Muscle Fibers, Skeletal - pathology Muscle, Skeletal - metabolism Muscle, Skeletal - pathology Ophthalmology Ophthalmoplegia Ophthalmoplegia, Chronic Progressive External - genetics Ophthalmoplegia, Chronic Progressive External - pathology Ophthalmoplegia, Chronic Progressive External - physiopathology Polymerase Chain Reaction Sequence Deletion |
title | Mitochondrial DNA defects in Brazilian patients with chronic progressive external ophthalmoplegia |
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