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The supposed tumor suppressor gene WWOX is mutated in an early lethal microcephaly syndrome with epilepsy, growth retardation and retinal degeneration
WWOX, encoding WW domain-containing oxidoreductase, spans FRA16D, the second most common chromosomal fragile site frequently altered in cancers. It is therefore considered a tumor suppressor gene, but its direct implication in cancerogenesis remains controversial. By whole-exome sequencing, we ident...
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| Published in: | Orphanet journal of rare diseases 2014-01, Vol.9 (1), p.12-12, Article 12 |
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| container_title | Orphanet journal of rare diseases |
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| creator | Abdel-Salam, Ghada Thoenes, Michaela Afifi, Hanan H Körber, Friederike Swan, Daniel Bolz, Hanno Jörn |
| description | WWOX, encoding WW domain-containing oxidoreductase, spans FRA16D, the second most common chromosomal fragile site frequently altered in cancers. It is therefore considered a tumor suppressor gene, but its direct implication in cancerogenesis remains controversial.
By whole-exome sequencing, we identified a homozygous WWOX nonsense mutation, p.Arg54*, in a girl from a consanguineous family with a severe syndrome of growth retardation, microcephaly, epileptic seizures, retinopathy and early death, a phenotype highly similar to the abormalities reported in lde/lde rats with a spontaneous functional null mutation of Wwox. As in rats, no tumors were observed in the patient or heterozygous mutation carriers.
Our finding, a homozygous loss-of-function germline mutation in WWOX in a patient with a lethal autosomal recessive syndrome, supports an alternative role of WWOX and indicates its importance for human viability. |
| doi_str_mv | 10.1186/1750-1172-9-12 |
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By whole-exome sequencing, we identified a homozygous WWOX nonsense mutation, p.Arg54*, in a girl from a consanguineous family with a severe syndrome of growth retardation, microcephaly, epileptic seizures, retinopathy and early death, a phenotype highly similar to the abormalities reported in lde/lde rats with a spontaneous functional null mutation of Wwox. As in rats, no tumors were observed in the patient or heterozygous mutation carriers.
Our finding, a homozygous loss-of-function germline mutation in WWOX in a patient with a lethal autosomal recessive syndrome, supports an alternative role of WWOX and indicates its importance for human viability.</description><identifier>ISSN: 1750-1172</identifier><identifier>EISSN: 1750-1172</identifier><identifier>DOI: 10.1186/1750-1172-9-12</identifier><identifier>PMID: 24456803</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Complications and side effects ; Epilepsy ; Epilepsy - genetics ; Gene mutations ; Genetic aspects ; Growth ; Humans ; Infant ; Medical research ; Microcephaly - genetics ; Mutation ; Oxidoreductases - genetics ; Physiological aspects ; Rare diseases ; Retinal degeneration ; Retinal Degeneration - genetics ; Risk factors ; Tumor Suppressor Proteins - genetics ; WW Domain-Containing Oxidoreductase</subject><ispartof>Orphanet journal of rare diseases, 2014-01, Vol.9 (1), p.12-12, Article 12</ispartof><rights>COPYRIGHT 2014 BioMed Central Ltd.</rights><rights>2014 Abdel-Salam et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</rights><rights>Copyright © 2014 Abdel-Salam et al.; licensee BioMed Central Ltd. 2014 Abdel-Salam et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b610t-36e77c529899b0d4e5e0a3cfcaa6714a54549ad096212f69500f52b5387d5e673</citedby><cites>FETCH-LOGICAL-b610t-36e77c529899b0d4e5e0a3cfcaa6714a54549ad096212f69500f52b5387d5e673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918143/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1496533539?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,315,733,786,790,891,25783,27957,27958,37047,37048,44625,53827,53829</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24456803$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abdel-Salam, Ghada</creatorcontrib><creatorcontrib>Thoenes, Michaela</creatorcontrib><creatorcontrib>Afifi, Hanan H</creatorcontrib><creatorcontrib>Körber, Friederike</creatorcontrib><creatorcontrib>Swan, Daniel</creatorcontrib><creatorcontrib>Bolz, Hanno Jörn</creatorcontrib><title>The supposed tumor suppressor gene WWOX is mutated in an early lethal microcephaly syndrome with epilepsy, growth retardation and retinal degeneration</title><title>Orphanet journal of rare diseases</title><addtitle>Orphanet J Rare Dis</addtitle><description>WWOX, encoding WW domain-containing oxidoreductase, spans FRA16D, the second most common chromosomal fragile site frequently altered in cancers. It is therefore considered a tumor suppressor gene, but its direct implication in cancerogenesis remains controversial.
By whole-exome sequencing, we identified a homozygous WWOX nonsense mutation, p.Arg54*, in a girl from a consanguineous family with a severe syndrome of growth retardation, microcephaly, epileptic seizures, retinopathy and early death, a phenotype highly similar to the abormalities reported in lde/lde rats with a spontaneous functional null mutation of Wwox. As in rats, no tumors were observed in the patient or heterozygous mutation carriers.
Our finding, a homozygous loss-of-function germline mutation in WWOX in a patient with a lethal autosomal recessive syndrome, supports an alternative role of WWOX and indicates its importance for human viability.</description><subject>Complications and side effects</subject><subject>Epilepsy</subject><subject>Epilepsy - genetics</subject><subject>Gene mutations</subject><subject>Genetic aspects</subject><subject>Growth</subject><subject>Humans</subject><subject>Infant</subject><subject>Medical research</subject><subject>Microcephaly - genetics</subject><subject>Mutation</subject><subject>Oxidoreductases - genetics</subject><subject>Physiological aspects</subject><subject>Rare diseases</subject><subject>Retinal degeneration</subject><subject>Retinal Degeneration - genetics</subject><subject>Risk factors</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>WW Domain-Containing Oxidoreductase</subject><issn>1750-1172</issn><issn>1750-1172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNqFkk1v1DAQhiMEomXhyhFZ4gISKXb8kfiCtKr4qFSpEhSVm-Ukk6yrJA62Q8kf4ffibMvShSLkg8eedx6P5nWSPCX4iJBCvCY5xykheZbKlGT3ksPdxf1b8UHyyPtLjBmnuHiYHGSMcVFgepj8ON8A8tM4Wg81ClNv3fbowPsYtjAAurg4-4KMR_0UdIgqMyA9INCum1EHYaM71JvK2QrGGM_Iz0PtbA_oyoQNgtF0MPr5FWqdvYoXDoJ2tQ7GLpx6OZshMmpYXnPbxOPkQaM7D09u9lXy-d3b8-MP6enZ-5Pj9WlaCoJDSgXkecUzWUhZ4poBB6xp1VRai5wwzRlnUtdYioxkjZAc44ZnJadFXnMQOV0lb66541T2UFcwBKc7NTrTazcrq43azwxmo1r7TVFJCsJoBKyvAaWx_wDsZyrbq8UXtfiipCJZZLy4acLZrxP4oHrjK-g6PYCdvCIcc0pZTvP_S5mUhFIeW1slz_-QXtrJxUFvVSISOZW_Va3uQJmhsbHLaoGqNWdYxKf5wjq6QxVXDdF5O0ATPd4veLlXEDUBvodWT96rk08f74THL-S9g2Y3PbJMqRB_z-vZbdN28l-_mv4ErZD33w</recordid><startdate>20140123</startdate><enddate>20140123</enddate><creator>Abdel-Salam, Ghada</creator><creator>Thoenes, Michaela</creator><creator>Afifi, Hanan H</creator><creator>Körber, Friederike</creator><creator>Swan, Daniel</creator><creator>Bolz, Hanno Jörn</creator><general>BioMed Central Ltd</general><general>BioMed Central</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>ISR</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20140123</creationdate><title>The supposed tumor suppressor gene WWOX is mutated in an early lethal microcephaly syndrome with epilepsy, growth retardation and retinal degeneration</title><author>Abdel-Salam, Ghada ; Thoenes, Michaela ; Afifi, Hanan H ; Körber, Friederike ; Swan, Daniel ; Bolz, Hanno Jörn</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b610t-36e77c529899b0d4e5e0a3cfcaa6714a54549ad096212f69500f52b5387d5e673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Complications and side effects</topic><topic>Epilepsy</topic><topic>Epilepsy - genetics</topic><topic>Gene mutations</topic><topic>Genetic aspects</topic><topic>Growth</topic><topic>Humans</topic><topic>Infant</topic><topic>Medical research</topic><topic>Microcephaly - genetics</topic><topic>Mutation</topic><topic>Oxidoreductases - genetics</topic><topic>Physiological aspects</topic><topic>Rare diseases</topic><topic>Retinal degeneration</topic><topic>Retinal Degeneration - genetics</topic><topic>Risk factors</topic><topic>Tumor Suppressor Proteins - genetics</topic><topic>WW Domain-Containing Oxidoreductase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abdel-Salam, Ghada</creatorcontrib><creatorcontrib>Thoenes, Michaela</creatorcontrib><creatorcontrib>Afifi, Hanan H</creatorcontrib><creatorcontrib>Körber, Friederike</creatorcontrib><creatorcontrib>Swan, Daniel</creatorcontrib><creatorcontrib>Bolz, Hanno Jörn</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Orphanet journal of rare diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abdel-Salam, Ghada</au><au>Thoenes, Michaela</au><au>Afifi, Hanan H</au><au>Körber, Friederike</au><au>Swan, Daniel</au><au>Bolz, Hanno Jörn</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The supposed tumor suppressor gene WWOX is mutated in an early lethal microcephaly syndrome with epilepsy, growth retardation and retinal degeneration</atitle><jtitle>Orphanet journal of rare diseases</jtitle><addtitle>Orphanet J Rare Dis</addtitle><date>2014-01-23</date><risdate>2014</risdate><volume>9</volume><issue>1</issue><spage>12</spage><epage>12</epage><pages>12-12</pages><artnum>12</artnum><issn>1750-1172</issn><eissn>1750-1172</eissn><notes>ObjectType-Case Study-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-4</notes><notes>content type line 23</notes><notes>ObjectType-Report-1</notes><notes>ObjectType-Article-3</notes><notes>ObjectType-Article-1</notes><notes>ObjectType-Feature-2</notes><abstract>WWOX, encoding WW domain-containing oxidoreductase, spans FRA16D, the second most common chromosomal fragile site frequently altered in cancers. It is therefore considered a tumor suppressor gene, but its direct implication in cancerogenesis remains controversial.
By whole-exome sequencing, we identified a homozygous WWOX nonsense mutation, p.Arg54*, in a girl from a consanguineous family with a severe syndrome of growth retardation, microcephaly, epileptic seizures, retinopathy and early death, a phenotype highly similar to the abormalities reported in lde/lde rats with a spontaneous functional null mutation of Wwox. As in rats, no tumors were observed in the patient or heterozygous mutation carriers.
Our finding, a homozygous loss-of-function germline mutation in WWOX in a patient with a lethal autosomal recessive syndrome, supports an alternative role of WWOX and indicates its importance for human viability.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>24456803</pmid><doi>10.1186/1750-1172-9-12</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | Publicly Available Content Database; PubMed Central |
| subjects | Complications and side effects Epilepsy Epilepsy - genetics Gene mutations Genetic aspects Growth Humans Infant Medical research Microcephaly - genetics Mutation Oxidoreductases - genetics Physiological aspects Rare diseases Retinal degeneration Retinal Degeneration - genetics Risk factors Tumor Suppressor Proteins - genetics WW Domain-Containing Oxidoreductase |
| title | The supposed tumor suppressor gene WWOX is mutated in an early lethal microcephaly syndrome with epilepsy, growth retardation and retinal degeneration |
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