A novel mutation in the XPA gene results in two truncated protein variants and leads to a severe XP/neurological symptoms phenotype
Background The nucleotide excision repair (NER) pathway repairs UV‐induced DNA lesions in an accurate fashion and prevents UV‐irradiated areas of the skin from tumour formation. The XPA protein plays a major role in DNA damage demarcation as well as stabilization of other NER factors and was found t...
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| Veröffentlicht in: | Journal of the European Academy of Dermatology and Venereology 2015-12, Vol.29 (12), p.2479-2482 |
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| container_title | Journal of the European Academy of Dermatology and Venereology |
| container_volume | 29 |
| creator | Lehmann, J. Schubert, S. Schäfer, A. Laspe, P. Haenssle, H.A. Ohlenbusch, A. Gratchev, A. Emmert, S. |
| description | Background
The nucleotide excision repair (NER) pathway repairs UV‐induced DNA lesions in an accurate fashion and prevents UV‐irradiated areas of the skin from tumour formation. The XPA protein plays a major role in DNA damage demarcation as well as stabilization of other NER factors and was found to be defective in xeroderma pigmentosum (XP) complementation group A patients.
Objective
Characterization of four new XP‐A patients.
Methods
Genomic and cDNA sequencing, post‐UV cell survival of living cells, host‐cell reactivation of patients' fibroblasts and Western blotting.
Results
One of the four investigated patients shows a novel mutation leading to two different truncated protein variants. Three patients contain the already described p.R228X mutation. All patient cell lines exhibit a strong UVC sensitivity and reduced NER capability. In most of the cases stable protein expression was detected.
Conclusion
We discovered four new XP‐A patients and a novel XPA mutation resulting in two diverse patient alleles. |
| doi_str_mv | 10.1111/jdv.12841 |
| format | Article |
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The nucleotide excision repair (NER) pathway repairs UV‐induced DNA lesions in an accurate fashion and prevents UV‐irradiated areas of the skin from tumour formation. The XPA protein plays a major role in DNA damage demarcation as well as stabilization of other NER factors and was found to be defective in xeroderma pigmentosum (XP) complementation group A patients.
Objective
Characterization of four new XP‐A patients.
Methods
Genomic and cDNA sequencing, post‐UV cell survival of living cells, host‐cell reactivation of patients' fibroblasts and Western blotting.
Results
One of the four investigated patients shows a novel mutation leading to two different truncated protein variants. Three patients contain the already described p.R228X mutation. All patient cell lines exhibit a strong UVC sensitivity and reduced NER capability. In most of the cases stable protein expression was detected.
Conclusion
We discovered four new XP‐A patients and a novel XPA mutation resulting in two diverse patient alleles.</description><identifier>ISSN: 0926-9959</identifier><identifier>EISSN: 1468-3083</identifier><identifier>DOI: 10.1111/jdv.12841</identifier><identifier>PMID: 25393472</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Adolescent ; Adult ; Child ; DNA Mutational Analysis ; DNA Repair - genetics ; Fibroblasts ; Humans ; Intellectual Disability - complications ; Intellectual Disability - genetics ; Male ; Mutation ; Phenotype ; Primary Cell Culture ; RNA, Messenger - analysis ; RNA, Messenger - metabolism ; Sequence Analysis, RNA ; Speech Disorders - complications ; Speech Disorders - genetics ; Xeroderma Pigmentosum - complications ; Xeroderma Pigmentosum - genetics ; Xeroderma Pigmentosum Group A Protein - chemistry ; Xeroderma Pigmentosum Group A Protein - genetics ; Young Adult</subject><ispartof>Journal of the European Academy of Dermatology and Venereology, 2015-12, Vol.29 (12), p.2479-2482</ispartof><rights>2014 European Academy of Dermatology and Venereology</rights><rights>2014 European Academy of Dermatology and Venereology.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3631-9643e5a6d857f23301e5181c053cc58787e1ccd072b4433ee849306ef3101feb3</citedby><cites>FETCH-LOGICAL-c3631-9643e5a6d857f23301e5181c053cc58787e1ccd072b4433ee849306ef3101feb3</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%2Fjdv.12841$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjdv.12841$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25393472$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lehmann, J.</creatorcontrib><creatorcontrib>Schubert, S.</creatorcontrib><creatorcontrib>Schäfer, A.</creatorcontrib><creatorcontrib>Laspe, P.</creatorcontrib><creatorcontrib>Haenssle, H.A.</creatorcontrib><creatorcontrib>Ohlenbusch, A.</creatorcontrib><creatorcontrib>Gratchev, A.</creatorcontrib><creatorcontrib>Emmert, S.</creatorcontrib><title>A novel mutation in the XPA gene results in two truncated protein variants and leads to a severe XP/neurological symptoms phenotype</title><title>Journal of the European Academy of Dermatology and Venereology</title><addtitle>J Eur Acad Dermatol Venereol</addtitle><description>Background
The nucleotide excision repair (NER) pathway repairs UV‐induced DNA lesions in an accurate fashion and prevents UV‐irradiated areas of the skin from tumour formation. The XPA protein plays a major role in DNA damage demarcation as well as stabilization of other NER factors and was found to be defective in xeroderma pigmentosum (XP) complementation group A patients.
Objective
Characterization of four new XP‐A patients.
Methods
Genomic and cDNA sequencing, post‐UV cell survival of living cells, host‐cell reactivation of patients' fibroblasts and Western blotting.
Results
One of the four investigated patients shows a novel mutation leading to two different truncated protein variants. Three patients contain the already described p.R228X mutation. All patient cell lines exhibit a strong UVC sensitivity and reduced NER capability. In most of the cases stable protein expression was detected.
Conclusion
We discovered four new XP‐A patients and a novel XPA mutation resulting in two diverse patient alleles.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Child</subject><subject>DNA Mutational Analysis</subject><subject>DNA Repair - genetics</subject><subject>Fibroblasts</subject><subject>Humans</subject><subject>Intellectual Disability - complications</subject><subject>Intellectual Disability - genetics</subject><subject>Male</subject><subject>Mutation</subject><subject>Phenotype</subject><subject>Primary Cell Culture</subject><subject>RNA, Messenger - analysis</subject><subject>RNA, Messenger - metabolism</subject><subject>Sequence Analysis, RNA</subject><subject>Speech Disorders - complications</subject><subject>Speech Disorders - genetics</subject><subject>Xeroderma Pigmentosum - complications</subject><subject>Xeroderma Pigmentosum - genetics</subject><subject>Xeroderma Pigmentosum Group A Protein - chemistry</subject><subject>Xeroderma Pigmentosum Group A Protein - genetics</subject><subject>Young Adult</subject><issn>0926-9959</issn><issn>1468-3083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1v1DAQhi0EokvhwB9APsIhXTtjJ85xtYUCKh8ShXKzvM6kTXHsYDtb9swfJ-22vTGXkUbP-2j0EvKSsyM-z_Kq3R7xUgn-iCy4qFQBTMFjsmBNWRVNI5sD8iylK8YY51I9JQelhAZEXS7I3xX1YYuODlM2uQ-e9p7mS6Q_v67oBXqkEdPkcrq9Xwea4-StydjSMYaM83VrYm_8TBjfUoemTTQHamjCLcYb0dLjFIMLF701jqbdMOYwJDpeog95N-Jz8qQzLuGLu31Ivr97e7Z-X5x-OfmwXp0WFirgRVMJQGmqVsm6KwEYR8kVt0yCtVLVqkZubcvqciMEAKISDbAKO-CMd7iBQ_J6750__z1hynrok0XnjMcwJc3riqlGcKFm9M0etTGkFLHTY-wHE3eaM33TuZ4717edz-yrO-20GbB9IO9LnoHlHrjuHe7-b9Ifj3_cK4t9ok8Z_zwkTPylqxpqqc8_n-hvcPZJiPW5ZvAPBmWbJw</recordid><startdate>201512</startdate><enddate>201512</enddate><creator>Lehmann, J.</creator><creator>Schubert, S.</creator><creator>Schäfer, A.</creator><creator>Laspe, P.</creator><creator>Haenssle, H.A.</creator><creator>Ohlenbusch, A.</creator><creator>Gratchev, A.</creator><creator>Emmert, S.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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>7X8</scope></search><sort><creationdate>201512</creationdate><title>A novel mutation in the XPA gene results in two truncated protein variants and leads to a severe XP/neurological symptoms phenotype</title><author>Lehmann, J. ; Schubert, S. ; Schäfer, A. ; Laspe, P. ; Haenssle, H.A. ; Ohlenbusch, A. ; Gratchev, A. ; Emmert, S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3631-9643e5a6d857f23301e5181c053cc58787e1ccd072b4433ee849306ef3101feb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Child</topic><topic>DNA Mutational Analysis</topic><topic>DNA Repair - genetics</topic><topic>Fibroblasts</topic><topic>Humans</topic><topic>Intellectual Disability - complications</topic><topic>Intellectual Disability - genetics</topic><topic>Male</topic><topic>Mutation</topic><topic>Phenotype</topic><topic>Primary Cell Culture</topic><topic>RNA, Messenger - analysis</topic><topic>RNA, Messenger - metabolism</topic><topic>Sequence Analysis, RNA</topic><topic>Speech Disorders - complications</topic><topic>Speech Disorders - genetics</topic><topic>Xeroderma Pigmentosum - complications</topic><topic>Xeroderma Pigmentosum - genetics</topic><topic>Xeroderma Pigmentosum Group A Protein - chemistry</topic><topic>Xeroderma Pigmentosum Group A Protein - genetics</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lehmann, J.</creatorcontrib><creatorcontrib>Schubert, S.</creatorcontrib><creatorcontrib>Schäfer, A.</creatorcontrib><creatorcontrib>Laspe, P.</creatorcontrib><creatorcontrib>Haenssle, H.A.</creatorcontrib><creatorcontrib>Ohlenbusch, A.</creatorcontrib><creatorcontrib>Gratchev, A.</creatorcontrib><creatorcontrib>Emmert, S.</creatorcontrib><collection>Istex</collection><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><jtitle>Journal of the European Academy of Dermatology and Venereology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lehmann, J.</au><au>Schubert, S.</au><au>Schäfer, A.</au><au>Laspe, P.</au><au>Haenssle, H.A.</au><au>Ohlenbusch, A.</au><au>Gratchev, A.</au><au>Emmert, S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel mutation in the XPA gene results in two truncated protein variants and leads to a severe XP/neurological symptoms phenotype</atitle><jtitle>Journal of the European Academy of Dermatology and Venereology</jtitle><addtitle>J Eur Acad Dermatol Venereol</addtitle><date>2015-12</date><risdate>2015</risdate><volume>29</volume><issue>12</issue><spage>2479</spage><epage>2482</epage><pages>2479-2482</pages><issn>0926-9959</issn><eissn>1468-3083</eissn><abstract>Background
The nucleotide excision repair (NER) pathway repairs UV‐induced DNA lesions in an accurate fashion and prevents UV‐irradiated areas of the skin from tumour formation. The XPA protein plays a major role in DNA damage demarcation as well as stabilization of other NER factors and was found to be defective in xeroderma pigmentosum (XP) complementation group A patients.
Objective
Characterization of four new XP‐A patients.
Methods
Genomic and cDNA sequencing, post‐UV cell survival of living cells, host‐cell reactivation of patients' fibroblasts and Western blotting.
Results
One of the four investigated patients shows a novel mutation leading to two different truncated protein variants. Three patients contain the already described p.R228X mutation. All patient cell lines exhibit a strong UVC sensitivity and reduced NER capability. In most of the cases stable protein expression was detected.
Conclusion
We discovered four new XP‐A patients and a novel XPA mutation resulting in two diverse patient alleles.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>25393472</pmid><doi>10.1111/jdv.12841</doi><tpages>4</tpages></addata></record> |
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| source | MEDLINE; Access via Wiley Online Library |
| subjects | Adolescent Adult Child DNA Mutational Analysis DNA Repair - genetics Fibroblasts Humans Intellectual Disability - complications Intellectual Disability - genetics Male Mutation Phenotype Primary Cell Culture RNA, Messenger - analysis RNA, Messenger - metabolism Sequence Analysis, RNA Speech Disorders - complications Speech Disorders - genetics Xeroderma Pigmentosum - complications Xeroderma Pigmentosum - genetics Xeroderma Pigmentosum Group A Protein - chemistry Xeroderma Pigmentosum Group A Protein - genetics Young Adult |
| title | A novel mutation in the XPA gene results in two truncated protein variants and leads to a severe XP/neurological symptoms phenotype |
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