Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia

Null mutations in the progranulin gene (GRN, PGRN) were recently identified as the causal mechanism underlying frontotemporal dementia (FTD) with ubiquitin‐positive brain pathology linked to chromosome 17 (FTDU‐17). In a Belgian and French FTD series comprising 332 patients, we reported 13 PGRN null...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Human mutation 2007-04, Vol.28 (4), p.416-416
Hauptverfasser: van der Zee, Julie, Le Ber, Isabelle, Maurer-Stroh, Sebastian, Engelborghs, Sebastiaan, Gijselinck, Ilse, Camuzat, Agnès, Brouwers, Nathalie, Vandenberghe, Rik, Sleegers, Kristel, Hannequin, Didier, Dermaut, Bart, Schymkowitz, Joost, Campion, Dominique, Santens, Patrick, Martin, Jean-Jacques, Lacomblez, Lucette, De Pooter, Tim, Peeters, Karin, Mattheijssens, Maria, Vercelletto, Martine, Van den Broeck, Marleen, Cruts, Marc, De Deyn, Peter P., Rousseau, Frederic, Brice, Alexis, Van Broeckhoven, Christine
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 416
container_issue 4
container_start_page 416
container_title Human mutation
container_volume 28
creator van der Zee, Julie
Le Ber, Isabelle
Maurer-Stroh, Sebastian
Engelborghs, Sebastiaan
Gijselinck, Ilse
Camuzat, Agnès
Brouwers, Nathalie
Vandenberghe, Rik
Sleegers, Kristel
Hannequin, Didier
Dermaut, Bart
Schymkowitz, Joost
Campion, Dominique
Santens, Patrick
Martin, Jean-Jacques
Lacomblez, Lucette
De Pooter, Tim
Peeters, Karin
Mattheijssens, Maria
Vercelletto, Martine
Van den Broeck, Marleen
Cruts, Marc
De Deyn, Peter P.
Rousseau, Frederic
Brice, Alexis
Van Broeckhoven, Christine
description Null mutations in the progranulin gene (GRN, PGRN) were recently identified as the causal mechanism underlying frontotemporal dementia (FTD) with ubiquitin‐positive brain pathology linked to chromosome 17 (FTDU‐17). In a Belgian and French FTD series comprising 332 patients, we reported 13 PGRN null mutations which were mainly nonsense and frameshift mutations resulting in premature stop codons. Here we report in the same patient series three missense mutations of which two (c.743C>T, p.Pro248Leu and c.1294C>T, p.Arg432Cys) were predicted in silico to severely affect protein folding and/or processing leading to PGRN protein haploinsufficiency. In addition, we observed three sequence variations in the 5' regulatory region that might potentially affect PGRN transcription activity. Our findings extend the mutation spectrum in PGRN leading to loss of functional PGRN as the basis for FTD. © 2007 Wiley‐Liss, Inc.
doi_str_mv 10.1002/humu.9484
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_70388107</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1231724291</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4854-81824731eca1207f6fe47dad1fdf02a962b1f46e2b6e421afeb41c21e6ffdc8a3</originalsourceid><addsrcrecordid>eNqFkV9rFDEUxQdRbK0--AUk-CD0Ydokk0kyj7JoV-lWBBfBl5CdudlNnUm2-YPttzfDLhUEES7kkvs7h5ucqnpN8AXBmF7u8pQvOibZk-qU4E7W5ZY9nfu2q4Xo2En1IsZbjLFs2-Z5dUJEw1qO6WllVznpZL2LyKcdBJR22iGXxxFNj5N98EPurdsijfY67fwWnO3R6GNRmXm8DbporEOlTPAu-QTT3gc9ogEmcMnql9Uzo8cIr47nWbX--OHbYllff7n6tHh_XfdMtqyWRFImGgK9JhQLww0wMeiBmMFgqjtON8QwDnTDgVGiDWwY6SkBbszQS92cVe8OvmWtuwwxqcnGHsZRO_A5KoEbKQkW_wUp5i0XvC3g27_AW5-DK49QpBNUcs5wgc4PUB_KtwQwah_spMODIljNKak5JTWnVNg3R8O8mWD4Qx5jKcDlAfhlR3j4t5Narlfro2V9UNiY4P5RocNPxUUjWvX95krdfP66kosfC7VsfgNjhq4x</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>197286640</pqid></control><display><type>article</type><title>Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>van der Zee, Julie ; Le Ber, Isabelle ; Maurer-Stroh, Sebastian ; Engelborghs, Sebastiaan ; Gijselinck, Ilse ; Camuzat, Agnès ; Brouwers, Nathalie ; Vandenberghe, Rik ; Sleegers, Kristel ; Hannequin, Didier ; Dermaut, Bart ; Schymkowitz, Joost ; Campion, Dominique ; Santens, Patrick ; Martin, Jean-Jacques ; Lacomblez, Lucette ; De Pooter, Tim ; Peeters, Karin ; Mattheijssens, Maria ; Vercelletto, Martine ; Van den Broeck, Marleen ; Cruts, Marc ; De Deyn, Peter P. ; Rousseau, Frederic ; Brice, Alexis ; Van Broeckhoven, Christine</creator><creatorcontrib>van der Zee, Julie ; Le Ber, Isabelle ; Maurer-Stroh, Sebastian ; Engelborghs, Sebastiaan ; Gijselinck, Ilse ; Camuzat, Agnès ; Brouwers, Nathalie ; Vandenberghe, Rik ; Sleegers, Kristel ; Hannequin, Didier ; Dermaut, Bart ; Schymkowitz, Joost ; Campion, Dominique ; Santens, Patrick ; Martin, Jean-Jacques ; Lacomblez, Lucette ; De Pooter, Tim ; Peeters, Karin ; Mattheijssens, Maria ; Vercelletto, Martine ; Van den Broeck, Marleen ; Cruts, Marc ; De Deyn, Peter P. ; Rousseau, Frederic ; Brice, Alexis ; Van Broeckhoven, Christine</creatorcontrib><description>Null mutations in the progranulin gene (GRN, PGRN) were recently identified as the causal mechanism underlying frontotemporal dementia (FTD) with ubiquitin‐positive brain pathology linked to chromosome 17 (FTDU‐17). In a Belgian and French FTD series comprising 332 patients, we reported 13 PGRN null mutations which were mainly nonsense and frameshift mutations resulting in premature stop codons. Here we report in the same patient series three missense mutations of which two (c.743C&gt;T, p.Pro248Leu and c.1294C&gt;T, p.Arg432Cys) were predicted in silico to severely affect protein folding and/or processing leading to PGRN protein haploinsufficiency. In addition, we observed three sequence variations in the 5' regulatory region that might potentially affect PGRN transcription activity. Our findings extend the mutation spectrum in PGRN leading to loss of functional PGRN as the basis for FTD. © 2007 Wiley‐Liss, Inc.</description><identifier>ISSN: 1059-7794</identifier><identifier>EISSN: 1098-1004</identifier><identifier>DOI: 10.1002/humu.9484</identifier><identifier>PMID: 17345602</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>17q21 ; Adult ; Aged ; Aged, 80 and over ; Amino Acid Sequence ; Case-Control Studies ; Conserved Sequence ; Dementia - genetics ; Dementia - metabolism ; Dementia - pathology ; DNA Mutational Analysis ; Female ; frontotemporal dementia ; GRN ; Humans ; Intercellular Signaling Peptides and Proteins - biosynthesis ; Intercellular Signaling Peptides and Proteins - deficiency ; Intercellular Signaling Peptides and Proteins - genetics ; Intercellular Signaling Peptides and Proteins - metabolism ; Male ; Microsatellite Repeats ; Middle Aged ; Molecular Sequence Data ; Mutation, Missense ; PGRN ; PGRN 5' sequence variations ; PGRN missense mutations ; progranulin ; Protein Conformation ; Protein Folding ; Protein Structure, Tertiary ; ubiquitin-positive inclusions</subject><ispartof>Human mutation, 2007-04, Vol.28 (4), p.416-416</ispartof><rights>2007 Wiley‐Liss, Inc.</rights><rights>Copyright 2007 Wiley-Liss, Inc.</rights><rights>Copyright © 2007 Wiley-Liss, Inc., A Wiley Company</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4854-81824731eca1207f6fe47dad1fdf02a962b1f46e2b6e421afeb41c21e6ffdc8a3</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.9484$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fhumu.9484$$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/17345602$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van der Zee, Julie</creatorcontrib><creatorcontrib>Le Ber, Isabelle</creatorcontrib><creatorcontrib>Maurer-Stroh, Sebastian</creatorcontrib><creatorcontrib>Engelborghs, Sebastiaan</creatorcontrib><creatorcontrib>Gijselinck, Ilse</creatorcontrib><creatorcontrib>Camuzat, Agnès</creatorcontrib><creatorcontrib>Brouwers, Nathalie</creatorcontrib><creatorcontrib>Vandenberghe, Rik</creatorcontrib><creatorcontrib>Sleegers, Kristel</creatorcontrib><creatorcontrib>Hannequin, Didier</creatorcontrib><creatorcontrib>Dermaut, Bart</creatorcontrib><creatorcontrib>Schymkowitz, Joost</creatorcontrib><creatorcontrib>Campion, Dominique</creatorcontrib><creatorcontrib>Santens, Patrick</creatorcontrib><creatorcontrib>Martin, Jean-Jacques</creatorcontrib><creatorcontrib>Lacomblez, Lucette</creatorcontrib><creatorcontrib>De Pooter, Tim</creatorcontrib><creatorcontrib>Peeters, Karin</creatorcontrib><creatorcontrib>Mattheijssens, Maria</creatorcontrib><creatorcontrib>Vercelletto, Martine</creatorcontrib><creatorcontrib>Van den Broeck, Marleen</creatorcontrib><creatorcontrib>Cruts, Marc</creatorcontrib><creatorcontrib>De Deyn, Peter P.</creatorcontrib><creatorcontrib>Rousseau, Frederic</creatorcontrib><creatorcontrib>Brice, Alexis</creatorcontrib><creatorcontrib>Van Broeckhoven, Christine</creatorcontrib><title>Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia</title><title>Human mutation</title><addtitle>Hum. Mutat</addtitle><description>Null mutations in the progranulin gene (GRN, PGRN) were recently identified as the causal mechanism underlying frontotemporal dementia (FTD) with ubiquitin‐positive brain pathology linked to chromosome 17 (FTDU‐17). In a Belgian and French FTD series comprising 332 patients, we reported 13 PGRN null mutations which were mainly nonsense and frameshift mutations resulting in premature stop codons. Here we report in the same patient series three missense mutations of which two (c.743C&gt;T, p.Pro248Leu and c.1294C&gt;T, p.Arg432Cys) were predicted in silico to severely affect protein folding and/or processing leading to PGRN protein haploinsufficiency. In addition, we observed three sequence variations in the 5' regulatory region that might potentially affect PGRN transcription activity. Our findings extend the mutation spectrum in PGRN leading to loss of functional PGRN as the basis for FTD. © 2007 Wiley‐Liss, Inc.</description><subject>17q21</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Amino Acid Sequence</subject><subject>Case-Control Studies</subject><subject>Conserved Sequence</subject><subject>Dementia - genetics</subject><subject>Dementia - metabolism</subject><subject>Dementia - pathology</subject><subject>DNA Mutational Analysis</subject><subject>Female</subject><subject>frontotemporal dementia</subject><subject>GRN</subject><subject>Humans</subject><subject>Intercellular Signaling Peptides and Proteins - biosynthesis</subject><subject>Intercellular Signaling Peptides and Proteins - deficiency</subject><subject>Intercellular Signaling Peptides and Proteins - genetics</subject><subject>Intercellular Signaling Peptides and Proteins - metabolism</subject><subject>Male</subject><subject>Microsatellite Repeats</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Mutation, Missense</subject><subject>PGRN</subject><subject>PGRN 5' sequence variations</subject><subject>PGRN missense mutations</subject><subject>progranulin</subject><subject>Protein Conformation</subject><subject>Protein Folding</subject><subject>Protein Structure, Tertiary</subject><subject>ubiquitin-positive inclusions</subject><issn>1059-7794</issn><issn>1098-1004</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkV9rFDEUxQdRbK0--AUk-CD0Ydokk0kyj7JoV-lWBBfBl5CdudlNnUm2-YPttzfDLhUEES7kkvs7h5ucqnpN8AXBmF7u8pQvOibZk-qU4E7W5ZY9nfu2q4Xo2En1IsZbjLFs2-Z5dUJEw1qO6WllVznpZL2LyKcdBJR22iGXxxFNj5N98EPurdsijfY67fwWnO3R6GNRmXm8DbporEOlTPAu-QTT3gc9ogEmcMnql9Uzo8cIr47nWbX--OHbYllff7n6tHh_XfdMtqyWRFImGgK9JhQLww0wMeiBmMFgqjtON8QwDnTDgVGiDWwY6SkBbszQS92cVe8OvmWtuwwxqcnGHsZRO_A5KoEbKQkW_wUp5i0XvC3g27_AW5-DK49QpBNUcs5wgc4PUB_KtwQwah_spMODIljNKak5JTWnVNg3R8O8mWD4Qx5jKcDlAfhlR3j4t5Narlfro2V9UNiY4P5RocNPxUUjWvX95krdfP66kosfC7VsfgNjhq4x</recordid><startdate>200704</startdate><enddate>200704</enddate><creator>van der Zee, Julie</creator><creator>Le Ber, Isabelle</creator><creator>Maurer-Stroh, Sebastian</creator><creator>Engelborghs, Sebastiaan</creator><creator>Gijselinck, Ilse</creator><creator>Camuzat, Agnès</creator><creator>Brouwers, Nathalie</creator><creator>Vandenberghe, Rik</creator><creator>Sleegers, Kristel</creator><creator>Hannequin, Didier</creator><creator>Dermaut, Bart</creator><creator>Schymkowitz, Joost</creator><creator>Campion, Dominique</creator><creator>Santens, Patrick</creator><creator>Martin, Jean-Jacques</creator><creator>Lacomblez, Lucette</creator><creator>De Pooter, Tim</creator><creator>Peeters, Karin</creator><creator>Mattheijssens, Maria</creator><creator>Vercelletto, Martine</creator><creator>Van den Broeck, Marleen</creator><creator>Cruts, Marc</creator><creator>De Deyn, Peter P.</creator><creator>Rousseau, Frederic</creator><creator>Brice, Alexis</creator><creator>Van Broeckhoven, Christine</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>AAYXX</scope><scope>CITATION</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>200704</creationdate><title>Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia</title><author>van der Zee, Julie ; Le Ber, Isabelle ; Maurer-Stroh, Sebastian ; Engelborghs, Sebastiaan ; Gijselinck, Ilse ; Camuzat, Agnès ; Brouwers, Nathalie ; Vandenberghe, Rik ; Sleegers, Kristel ; Hannequin, Didier ; Dermaut, Bart ; Schymkowitz, Joost ; Campion, Dominique ; Santens, Patrick ; Martin, Jean-Jacques ; Lacomblez, Lucette ; De Pooter, Tim ; Peeters, Karin ; Mattheijssens, Maria ; Vercelletto, Martine ; Van den Broeck, Marleen ; Cruts, Marc ; De Deyn, Peter P. ; Rousseau, Frederic ; Brice, Alexis ; Van Broeckhoven, Christine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4854-81824731eca1207f6fe47dad1fdf02a962b1f46e2b6e421afeb41c21e6ffdc8a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>17q21</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Amino Acid Sequence</topic><topic>Case-Control Studies</topic><topic>Conserved Sequence</topic><topic>Dementia - genetics</topic><topic>Dementia - metabolism</topic><topic>Dementia - pathology</topic><topic>DNA Mutational Analysis</topic><topic>Female</topic><topic>frontotemporal dementia</topic><topic>GRN</topic><topic>Humans</topic><topic>Intercellular Signaling Peptides and Proteins - biosynthesis</topic><topic>Intercellular Signaling Peptides and Proteins - deficiency</topic><topic>Intercellular Signaling Peptides and Proteins - genetics</topic><topic>Intercellular Signaling Peptides and Proteins - metabolism</topic><topic>Male</topic><topic>Microsatellite Repeats</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Mutation, Missense</topic><topic>PGRN</topic><topic>PGRN 5' sequence variations</topic><topic>PGRN missense mutations</topic><topic>progranulin</topic><topic>Protein Conformation</topic><topic>Protein Folding</topic><topic>Protein Structure, Tertiary</topic><topic>ubiquitin-positive inclusions</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van der Zee, Julie</creatorcontrib><creatorcontrib>Le Ber, Isabelle</creatorcontrib><creatorcontrib>Maurer-Stroh, Sebastian</creatorcontrib><creatorcontrib>Engelborghs, Sebastiaan</creatorcontrib><creatorcontrib>Gijselinck, Ilse</creatorcontrib><creatorcontrib>Camuzat, Agnès</creatorcontrib><creatorcontrib>Brouwers, Nathalie</creatorcontrib><creatorcontrib>Vandenberghe, Rik</creatorcontrib><creatorcontrib>Sleegers, Kristel</creatorcontrib><creatorcontrib>Hannequin, Didier</creatorcontrib><creatorcontrib>Dermaut, Bart</creatorcontrib><creatorcontrib>Schymkowitz, Joost</creatorcontrib><creatorcontrib>Campion, Dominique</creatorcontrib><creatorcontrib>Santens, Patrick</creatorcontrib><creatorcontrib>Martin, Jean-Jacques</creatorcontrib><creatorcontrib>Lacomblez, Lucette</creatorcontrib><creatorcontrib>De Pooter, Tim</creatorcontrib><creatorcontrib>Peeters, Karin</creatorcontrib><creatorcontrib>Mattheijssens, Maria</creatorcontrib><creatorcontrib>Vercelletto, Martine</creatorcontrib><creatorcontrib>Van den Broeck, Marleen</creatorcontrib><creatorcontrib>Cruts, Marc</creatorcontrib><creatorcontrib>De Deyn, Peter P.</creatorcontrib><creatorcontrib>Rousseau, Frederic</creatorcontrib><creatorcontrib>Brice, Alexis</creatorcontrib><creatorcontrib>Van Broeckhoven, Christine</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>ProQuest Central (Corporate)</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health &amp; 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 &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Access via ProQuest (Open Access)</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>van der Zee, Julie</au><au>Le Ber, Isabelle</au><au>Maurer-Stroh, Sebastian</au><au>Engelborghs, Sebastiaan</au><au>Gijselinck, Ilse</au><au>Camuzat, Agnès</au><au>Brouwers, Nathalie</au><au>Vandenberghe, Rik</au><au>Sleegers, Kristel</au><au>Hannequin, Didier</au><au>Dermaut, Bart</au><au>Schymkowitz, Joost</au><au>Campion, Dominique</au><au>Santens, Patrick</au><au>Martin, Jean-Jacques</au><au>Lacomblez, Lucette</au><au>De Pooter, Tim</au><au>Peeters, Karin</au><au>Mattheijssens, Maria</au><au>Vercelletto, Martine</au><au>Van den Broeck, Marleen</au><au>Cruts, Marc</au><au>De Deyn, Peter P.</au><au>Rousseau, Frederic</au><au>Brice, Alexis</au><au>Van Broeckhoven, Christine</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia</atitle><jtitle>Human mutation</jtitle><addtitle>Hum. Mutat</addtitle><date>2007-04</date><risdate>2007</risdate><volume>28</volume><issue>4</issue><spage>416</spage><epage>416</epage><pages>416-416</pages><issn>1059-7794</issn><eissn>1098-1004</eissn><abstract>Null mutations in the progranulin gene (GRN, PGRN) were recently identified as the causal mechanism underlying frontotemporal dementia (FTD) with ubiquitin‐positive brain pathology linked to chromosome 17 (FTDU‐17). In a Belgian and French FTD series comprising 332 patients, we reported 13 PGRN null mutations which were mainly nonsense and frameshift mutations resulting in premature stop codons. Here we report in the same patient series three missense mutations of which two (c.743C&gt;T, p.Pro248Leu and c.1294C&gt;T, p.Arg432Cys) were predicted in silico to severely affect protein folding and/or processing leading to PGRN protein haploinsufficiency. In addition, we observed three sequence variations in the 5' regulatory region that might potentially affect PGRN transcription activity. Our findings extend the mutation spectrum in PGRN leading to loss of functional PGRN as the basis for FTD. © 2007 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>17345602</pmid><doi>10.1002/humu.9484</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1059-7794
ispartof Human mutation, 2007-04, Vol.28 (4), p.416-416
issn 1059-7794
1098-1004
language eng
recordid cdi_proquest_miscellaneous_70388107
source MEDLINE; Access via Wiley Online Library
subjects 17q21
Adult
Aged
Aged, 80 and over
Amino Acid Sequence
Case-Control Studies
Conserved Sequence
Dementia - genetics
Dementia - metabolism
Dementia - pathology
DNA Mutational Analysis
Female
frontotemporal dementia
GRN
Humans
Intercellular Signaling Peptides and Proteins - biosynthesis
Intercellular Signaling Peptides and Proteins - deficiency
Intercellular Signaling Peptides and Proteins - genetics
Intercellular Signaling Peptides and Proteins - metabolism
Male
Microsatellite Repeats
Middle Aged
Molecular Sequence Data
Mutation, Missense
PGRN
PGRN 5' sequence variations
PGRN missense mutations
progranulin
Protein Conformation
Protein Folding
Protein Structure, Tertiary
ubiquitin-positive inclusions
title Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T15%3A50%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mutations%20other%20than%20null%20mutations%20producing%20a%20pathogenic%20loss%20of%20progranulin%20in%20frontotemporal%20dementia&rft.jtitle=Human%20mutation&rft.au=van%20der%20Zee,%20Julie&rft.date=2007-04&rft.volume=28&rft.issue=4&rft.spage=416&rft.epage=416&rft.pages=416-416&rft.issn=1059-7794&rft.eissn=1098-1004&rft_id=info:doi/10.1002/humu.9484&rft_dat=%3Cproquest_cross%3E1231724291%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=197286640&rft_id=info:pmid/17345602&rfr_iscdi=true