The role of cathepsin C in Papillon-Lefèvre syndrome, prepubertal periodontitis, and aggressive periodontitis
We have previously reported that loss‐of‐function mutations in the cathepsin C gene (CTSC) result in Papillon‐Lefèvre syndrome, an autosomal recessive condition characterized by palmoplantar keratosis and early‐onset, severe periodontitis. Others have also reported CTSC mutations in patients with se...
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| Veröffentlicht in: | Human mutation 2004-03, Vol.23 (3), p.222-228 |
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| creator | Hewitt, Chelsee McCormick, Derek Linden, Gerry Turk, Dusan Stern, Igor Wallace, Ian Southern, Louise Zhang, Liqun Howard, Rebecca Bullon, Pedro Wong, Melanie Widmer, Richard Gaffar, Khaled Abdul Awawdeh, Lama Briggs, Jim Yaghmai, Reza Jabs, Ethlin W. Hoeger, Peter Bleck, Oliver Rüdiger, Stefan G. Petersilka, Gregor Battino, Maurizio Brett, Peter Hattab, Faiez Al-Hamed, Mohamed Sloan, Philip Toomes, Carmel Dixon, Mike James, Jacqueline Read, Andrew P. Thakker, Nalin |
| description | We have previously reported that loss‐of‐function mutations in the cathepsin C gene (CTSC) result in Papillon‐Lefèvre syndrome, an autosomal recessive condition characterized by palmoplantar keratosis and early‐onset, severe periodontitis. Others have also reported CTSC mutations in patients with severe prepubertal periodontitis, but without any skin manifestations. The possible role of CTSC variants in more common types of non‐mendelian, early‐onset, severe periodontitis (“aggressive periodontitis”) has not been investigated. In this study, we have investigated the role of CTSC in all three conditions. We demonstrate that PLS is genetically homogeneous and the mutation spectrum that includes three novel mutations (c.386T>A/p.V129E, c.935A>G/p.Q312R, and c.1235A>G/p.Y412C) in 21 PLS families (including eight from our previous study) provides an insight into structure–function relationships of CTSC. Our data also suggest that a complete loss‐of‐function appears to be necessary for the manifestation of the phenotype, making it unlikely that weak CTSC mutations are a cause of aggressive periodontitis. This was confirmed by analyses of the CTSC activity in 30 subjects with aggressive periodontitis and age–sex matched controls, which demonstrated that there was no significant difference between these two groups (1,728.7 ± SD 576.8 μ moles/mg/min vs. 1,678.7 ± SD 527.2 μ moles/mg/min, respectively, p = 0.73). CTSC mutations were detected in only one of two families with prepubertal periodontitis; these did not form a separate functional class with respect to those observed in classical PLS. The affected individuals in the other prepubertal periodontitis family not only lacked CTSC mutations, but in addition did not share the haplotypes at the CTSC locus. These data suggest that prepubertal periodontitis is a genetically heterogeneous disease that, in some families, just represents a partially penetrant PLS. Hum Mutat 23:222–228, 2004. © 2004 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/humu.10314 |
| format | Article |
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Others have also reported CTSC mutations in patients with severe prepubertal periodontitis, but without any skin manifestations. The possible role of CTSC variants in more common types of non‐mendelian, early‐onset, severe periodontitis (“aggressive periodontitis”) has not been investigated. In this study, we have investigated the role of CTSC in all three conditions. We demonstrate that PLS is genetically homogeneous and the mutation spectrum that includes three novel mutations (c.386T>A/p.V129E, c.935A>G/p.Q312R, and c.1235A>G/p.Y412C) in 21 PLS families (including eight from our previous study) provides an insight into structure–function relationships of CTSC. Our data also suggest that a complete loss‐of‐function appears to be necessary for the manifestation of the phenotype, making it unlikely that weak CTSC mutations are a cause of aggressive periodontitis. This was confirmed by analyses of the CTSC activity in 30 subjects with aggressive periodontitis and age–sex matched controls, which demonstrated that there was no significant difference between these two groups (1,728.7 ± SD 576.8 μ moles/mg/min vs. 1,678.7 ± SD 527.2 μ moles/mg/min, respectively, p = 0.73). CTSC mutations were detected in only one of two families with prepubertal periodontitis; these did not form a separate functional class with respect to those observed in classical PLS. The affected individuals in the other prepubertal periodontitis family not only lacked CTSC mutations, but in addition did not share the haplotypes at the CTSC locus. These data suggest that prepubertal periodontitis is a genetically heterogeneous disease that, in some families, just represents a partially penetrant PLS. Hum Mutat 23:222–228, 2004. © 2004 Wiley‐Liss, Inc.</description><identifier>ISSN: 1059-7794</identifier><identifier>EISSN: 1098-1004</identifier><identifier>DOI: 10.1002/humu.10314</identifier><identifier>PMID: 14974080</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adult ; Aggressive Periodontitis - genetics ; cathepsin C ; Cathepsin C - genetics ; Cathepsin C - physiology ; CTSC ; DNA Mutational Analysis - methods ; Female ; Genetic Markers - genetics ; Genotype ; Haplotypes - genetics ; Humans ; Male ; Models, Molecular ; Mutation, Missense - genetics ; Papillon-Lefevre Disease - genetics ; Papillon-Lefèvre syndrome ; Pedigree ; periodontitis ; Periodontitis - genetics ; PLS ; Point Mutation - genetics ; Polymorphism, Genetic - genetics ; Protein Structure, Tertiary - genetics</subject><ispartof>Human mutation, 2004-03, Vol.23 (3), p.222-228</ispartof><rights>Copyright © 2004 Wiley‐Liss, Inc.</rights><rights>Copyright 2004 Wiley-Liss, Inc.</rights><rights>Copyright © 2004 Wiley-Liss, Inc., A Wiley Company</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4594-bd282945b00bdda20b2500355cc48723b1bb5082358905dee5412a6cefaccd3f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fhumu.10314$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fhumu.10314$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14974080$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hewitt, Chelsee</creatorcontrib><creatorcontrib>McCormick, Derek</creatorcontrib><creatorcontrib>Linden, Gerry</creatorcontrib><creatorcontrib>Turk, Dusan</creatorcontrib><creatorcontrib>Stern, Igor</creatorcontrib><creatorcontrib>Wallace, Ian</creatorcontrib><creatorcontrib>Southern, Louise</creatorcontrib><creatorcontrib>Zhang, Liqun</creatorcontrib><creatorcontrib>Howard, Rebecca</creatorcontrib><creatorcontrib>Bullon, Pedro</creatorcontrib><creatorcontrib>Wong, Melanie</creatorcontrib><creatorcontrib>Widmer, Richard</creatorcontrib><creatorcontrib>Gaffar, Khaled Abdul</creatorcontrib><creatorcontrib>Awawdeh, Lama</creatorcontrib><creatorcontrib>Briggs, Jim</creatorcontrib><creatorcontrib>Yaghmai, Reza</creatorcontrib><creatorcontrib>Jabs, Ethlin W.</creatorcontrib><creatorcontrib>Hoeger, Peter</creatorcontrib><creatorcontrib>Bleck, Oliver</creatorcontrib><creatorcontrib>Rüdiger, Stefan G.</creatorcontrib><creatorcontrib>Petersilka, Gregor</creatorcontrib><creatorcontrib>Battino, Maurizio</creatorcontrib><creatorcontrib>Brett, Peter</creatorcontrib><creatorcontrib>Hattab, Faiez</creatorcontrib><creatorcontrib>Al-Hamed, Mohamed</creatorcontrib><creatorcontrib>Sloan, Philip</creatorcontrib><creatorcontrib>Toomes, Carmel</creatorcontrib><creatorcontrib>Dixon, Mike</creatorcontrib><creatorcontrib>James, Jacqueline</creatorcontrib><creatorcontrib>Read, Andrew P.</creatorcontrib><creatorcontrib>Thakker, Nalin</creatorcontrib><title>The role of cathepsin C in Papillon-Lefèvre syndrome, prepubertal periodontitis, and aggressive periodontitis</title><title>Human mutation</title><addtitle>Hum. Mutat</addtitle><description>We have previously reported that loss‐of‐function mutations in the cathepsin C gene (CTSC) result in Papillon‐Lefèvre syndrome, an autosomal recessive condition characterized by palmoplantar keratosis and early‐onset, severe periodontitis. Others have also reported CTSC mutations in patients with severe prepubertal periodontitis, but without any skin manifestations. The possible role of CTSC variants in more common types of non‐mendelian, early‐onset, severe periodontitis (“aggressive periodontitis”) has not been investigated. In this study, we have investigated the role of CTSC in all three conditions. We demonstrate that PLS is genetically homogeneous and the mutation spectrum that includes three novel mutations (c.386T>A/p.V129E, c.935A>G/p.Q312R, and c.1235A>G/p.Y412C) in 21 PLS families (including eight from our previous study) provides an insight into structure–function relationships of CTSC. Our data also suggest that a complete loss‐of‐function appears to be necessary for the manifestation of the phenotype, making it unlikely that weak CTSC mutations are a cause of aggressive periodontitis. This was confirmed by analyses of the CTSC activity in 30 subjects with aggressive periodontitis and age–sex matched controls, which demonstrated that there was no significant difference between these two groups (1,728.7 ± SD 576.8 μ moles/mg/min vs. 1,678.7 ± SD 527.2 μ moles/mg/min, respectively, p = 0.73). CTSC mutations were detected in only one of two families with prepubertal periodontitis; these did not form a separate functional class with respect to those observed in classical PLS. The affected individuals in the other prepubertal periodontitis family not only lacked CTSC mutations, but in addition did not share the haplotypes at the CTSC locus. These data suggest that prepubertal periodontitis is a genetically heterogeneous disease that, in some families, just represents a partially penetrant PLS. Hum Mutat 23:222–228, 2004. © 2004 Wiley‐Liss, Inc.</description><subject>Adult</subject><subject>Aggressive Periodontitis - genetics</subject><subject>cathepsin C</subject><subject>Cathepsin C - genetics</subject><subject>Cathepsin C - physiology</subject><subject>CTSC</subject><subject>DNA Mutational Analysis - methods</subject><subject>Female</subject><subject>Genetic Markers - genetics</subject><subject>Genotype</subject><subject>Haplotypes - genetics</subject><subject>Humans</subject><subject>Male</subject><subject>Models, Molecular</subject><subject>Mutation, Missense - genetics</subject><subject>Papillon-Lefevre Disease - genetics</subject><subject>Papillon-Lefèvre syndrome</subject><subject>Pedigree</subject><subject>periodontitis</subject><subject>Periodontitis - genetics</subject><subject>PLS</subject><subject>Point Mutation - genetics</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Protein Structure, Tertiary - genetics</subject><issn>1059-7794</issn><issn>1098-1004</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkc1u1DAUhS0EoqWw4QGQxYJVA9d_tbOEEZ1STYFFR11aTnzTcUniYCeFeSPegxcj0ykg2NhHPt-5uvIh5DmD1wyAv9lM3TQrweQDcsigNMX8LB_utCoLrUt5QJ7kfAMARinxmBwwWWoJBg5Jf7lBmmKLNDa0duMGhxx6uqDz8dkNoW1jX6yw-fnjNiHN296n2OExHRIOU4VpdC0dMIXoYz-GMeRj6npP3fV1wpzDLf7rPiWPGtdmfHZ_H5H16fvLxVmx-rT8sHi7KmqpSllUnhteSlUBVN47DhVXAEKpupZGc1GxqlJguFCmBOURlWTcndTYuLr2ohFH5NV-7pDi1wnzaLuQa2xb12OcsjXANOdQzuDL_8CbOKV-3s2yUnOttDIz9OIemqoOvR1S6Fza2t_fOANsD3wLLW7_-mB3BdldQfauIHu2vljfqTlT7DMhj_j9T8alL_ZEC63s1celFReny6t36tyei1_ThZP_</recordid><startdate>200403</startdate><enddate>200403</enddate><creator>Hewitt, Chelsee</creator><creator>McCormick, Derek</creator><creator>Linden, Gerry</creator><creator>Turk, Dusan</creator><creator>Stern, Igor</creator><creator>Wallace, Ian</creator><creator>Southern, Louise</creator><creator>Zhang, Liqun</creator><creator>Howard, Rebecca</creator><creator>Bullon, Pedro</creator><creator>Wong, Melanie</creator><creator>Widmer, Richard</creator><creator>Gaffar, Khaled Abdul</creator><creator>Awawdeh, Lama</creator><creator>Briggs, Jim</creator><creator>Yaghmai, Reza</creator><creator>Jabs, Ethlin W.</creator><creator>Hoeger, Peter</creator><creator>Bleck, Oliver</creator><creator>Rüdiger, Stefan G.</creator><creator>Petersilka, Gregor</creator><creator>Battino, Maurizio</creator><creator>Brett, Peter</creator><creator>Hattab, Faiez</creator><creator>Al-Hamed, Mohamed</creator><creator>Sloan, Philip</creator><creator>Toomes, Carmel</creator><creator>Dixon, Mike</creator><creator>James, Jacqueline</creator><creator>Read, Andrew P.</creator><creator>Thakker, Nalin</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Hindawi Limited</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200403</creationdate><title>The role of cathepsin C in Papillon-Lefèvre syndrome, prepubertal periodontitis, and aggressive periodontitis</title><author>Hewitt, Chelsee ; McCormick, Derek ; Linden, Gerry ; Turk, Dusan ; Stern, Igor ; Wallace, Ian ; Southern, Louise ; Zhang, Liqun ; Howard, Rebecca ; Bullon, Pedro ; Wong, Melanie ; Widmer, Richard ; Gaffar, Khaled Abdul ; Awawdeh, Lama ; Briggs, Jim ; Yaghmai, Reza ; Jabs, Ethlin W. ; Hoeger, Peter ; Bleck, Oliver ; Rüdiger, Stefan G. ; Petersilka, Gregor ; Battino, Maurizio ; Brett, Peter ; Hattab, Faiez ; Al-Hamed, Mohamed ; Sloan, Philip ; Toomes, Carmel ; Dixon, Mike ; James, Jacqueline ; Read, Andrew P. ; Thakker, Nalin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4594-bd282945b00bdda20b2500355cc48723b1bb5082358905dee5412a6cefaccd3f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adult</topic><topic>Aggressive Periodontitis - genetics</topic><topic>cathepsin C</topic><topic>Cathepsin C - genetics</topic><topic>Cathepsin C - physiology</topic><topic>CTSC</topic><topic>DNA Mutational Analysis - methods</topic><topic>Female</topic><topic>Genetic Markers - genetics</topic><topic>Genotype</topic><topic>Haplotypes - genetics</topic><topic>Humans</topic><topic>Male</topic><topic>Models, Molecular</topic><topic>Mutation, Missense - genetics</topic><topic>Papillon-Lefevre Disease - genetics</topic><topic>Papillon-Lefèvre syndrome</topic><topic>Pedigree</topic><topic>periodontitis</topic><topic>Periodontitis - genetics</topic><topic>PLS</topic><topic>Point Mutation - genetics</topic><topic>Polymorphism, Genetic - genetics</topic><topic>Protein Structure, Tertiary - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hewitt, Chelsee</creatorcontrib><creatorcontrib>McCormick, Derek</creatorcontrib><creatorcontrib>Linden, Gerry</creatorcontrib><creatorcontrib>Turk, Dusan</creatorcontrib><creatorcontrib>Stern, Igor</creatorcontrib><creatorcontrib>Wallace, Ian</creatorcontrib><creatorcontrib>Southern, Louise</creatorcontrib><creatorcontrib>Zhang, Liqun</creatorcontrib><creatorcontrib>Howard, Rebecca</creatorcontrib><creatorcontrib>Bullon, Pedro</creatorcontrib><creatorcontrib>Wong, Melanie</creatorcontrib><creatorcontrib>Widmer, Richard</creatorcontrib><creatorcontrib>Gaffar, Khaled Abdul</creatorcontrib><creatorcontrib>Awawdeh, Lama</creatorcontrib><creatorcontrib>Briggs, Jim</creatorcontrib><creatorcontrib>Yaghmai, Reza</creatorcontrib><creatorcontrib>Jabs, Ethlin W.</creatorcontrib><creatorcontrib>Hoeger, Peter</creatorcontrib><creatorcontrib>Bleck, Oliver</creatorcontrib><creatorcontrib>Rüdiger, Stefan G.</creatorcontrib><creatorcontrib>Petersilka, Gregor</creatorcontrib><creatorcontrib>Battino, Maurizio</creatorcontrib><creatorcontrib>Brett, Peter</creatorcontrib><creatorcontrib>Hattab, Faiez</creatorcontrib><creatorcontrib>Al-Hamed, Mohamed</creatorcontrib><creatorcontrib>Sloan, Philip</creatorcontrib><creatorcontrib>Toomes, Carmel</creatorcontrib><creatorcontrib>Dixon, Mike</creatorcontrib><creatorcontrib>James, Jacqueline</creatorcontrib><creatorcontrib>Read, Andrew P.</creatorcontrib><creatorcontrib>Thakker, Nalin</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Human mutation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hewitt, Chelsee</au><au>McCormick, Derek</au><au>Linden, Gerry</au><au>Turk, Dusan</au><au>Stern, Igor</au><au>Wallace, Ian</au><au>Southern, Louise</au><au>Zhang, Liqun</au><au>Howard, Rebecca</au><au>Bullon, Pedro</au><au>Wong, Melanie</au><au>Widmer, Richard</au><au>Gaffar, Khaled Abdul</au><au>Awawdeh, Lama</au><au>Briggs, Jim</au><au>Yaghmai, Reza</au><au>Jabs, Ethlin W.</au><au>Hoeger, Peter</au><au>Bleck, Oliver</au><au>Rüdiger, Stefan G.</au><au>Petersilka, Gregor</au><au>Battino, Maurizio</au><au>Brett, Peter</au><au>Hattab, Faiez</au><au>Al-Hamed, Mohamed</au><au>Sloan, Philip</au><au>Toomes, Carmel</au><au>Dixon, Mike</au><au>James, Jacqueline</au><au>Read, Andrew P.</au><au>Thakker, Nalin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The role of cathepsin C in Papillon-Lefèvre syndrome, prepubertal periodontitis, and aggressive periodontitis</atitle><jtitle>Human mutation</jtitle><addtitle>Hum. Mutat</addtitle><date>2004-03</date><risdate>2004</risdate><volume>23</volume><issue>3</issue><spage>222</spage><epage>228</epage><pages>222-228</pages><issn>1059-7794</issn><eissn>1098-1004</eissn><abstract>We have previously reported that loss‐of‐function mutations in the cathepsin C gene (CTSC) result in Papillon‐Lefèvre syndrome, an autosomal recessive condition characterized by palmoplantar keratosis and early‐onset, severe periodontitis. Others have also reported CTSC mutations in patients with severe prepubertal periodontitis, but without any skin manifestations. The possible role of CTSC variants in more common types of non‐mendelian, early‐onset, severe periodontitis (“aggressive periodontitis”) has not been investigated. In this study, we have investigated the role of CTSC in all three conditions. We demonstrate that PLS is genetically homogeneous and the mutation spectrum that includes three novel mutations (c.386T>A/p.V129E, c.935A>G/p.Q312R, and c.1235A>G/p.Y412C) in 21 PLS families (including eight from our previous study) provides an insight into structure–function relationships of CTSC. Our data also suggest that a complete loss‐of‐function appears to be necessary for the manifestation of the phenotype, making it unlikely that weak CTSC mutations are a cause of aggressive periodontitis. This was confirmed by analyses of the CTSC activity in 30 subjects with aggressive periodontitis and age–sex matched controls, which demonstrated that there was no significant difference between these two groups (1,728.7 ± SD 576.8 μ moles/mg/min vs. 1,678.7 ± SD 527.2 μ moles/mg/min, respectively, p = 0.73). CTSC mutations were detected in only one of two families with prepubertal periodontitis; these did not form a separate functional class with respect to those observed in classical PLS. The affected individuals in the other prepubertal periodontitis family not only lacked CTSC mutations, but in addition did not share the haplotypes at the CTSC locus. These data suggest that prepubertal periodontitis is a genetically heterogeneous disease that, in some families, just represents a partially penetrant PLS. Hum Mutat 23:222–228, 2004. © 2004 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>14974080</pmid><doi>10.1002/humu.10314</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_proquest_miscellaneous_80172209 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adult Aggressive Periodontitis - genetics cathepsin C Cathepsin C - genetics Cathepsin C - physiology CTSC DNA Mutational Analysis - methods Female Genetic Markers - genetics Genotype Haplotypes - genetics Humans Male Models, Molecular Mutation, Missense - genetics Papillon-Lefevre Disease - genetics Papillon-Lefèvre syndrome Pedigree periodontitis Periodontitis - genetics PLS Point Mutation - genetics Polymorphism, Genetic - genetics Protein Structure, Tertiary - genetics |
| title | The role of cathepsin C in Papillon-Lefèvre syndrome, prepubertal periodontitis, and aggressive periodontitis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T17%3A02%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20role%20of%20cathepsin%20C%20in%20Papillon-Lef%C3%A8vre%20syndrome,%20prepubertal%20periodontitis,%20and%20aggressive%20periodontitis&rft.jtitle=Human%20mutation&rft.au=Hewitt,%20Chelsee&rft.date=2004-03&rft.volume=23&rft.issue=3&rft.spage=222&rft.epage=228&rft.pages=222-228&rft.issn=1059-7794&rft.eissn=1098-1004&rft_id=info:doi/10.1002/humu.10314&rft_dat=%3Cproquest_pubme%3E80172209%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=197275758&rft_id=info:pmid/14974080&rfr_iscdi=true |