R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation.
Identifieur interne : 001993 ( Ncbi/Merge ); précédent : 001992; suivant : 001994R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation.
Auteurs : William C. Nichols [États-Unis] ; Diane K. Marek ; Michael W. Pauciulo ; Nathan Pankratz ; Cheryl A. Halter ; Alice Rudolph ; Clifford W. Shults ; Joanne Wojcieszek ; Tatiana ForoudSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2007.
English descriptors
- KwdEn :
- Adenine Nucleotide Translocator 1 (genetics), Adolescent, Adult, Aged, Aged, 80 and over, Amino Acid Substitution (genetics), Arginine (genetics), Carrier Proteins (genetics), Diagnosis, Differential, Female, Genetic Variation (genetics), Genotype, Humans, Male, Middle Aged, Parkinson Disease (diagnosis), Parkinson Disease (genetics), Point Mutation (genetics), Protein-Serine-Threonine Kinases (genetics).
- MESH :
- chemical , genetics : Adenine Nucleotide Translocator 1, Arginine, Carrier Proteins, Protein-Serine-Threonine Kinases.
- diagnosis : Parkinson Disease.
- genetics : Amino Acid Substitution, Genetic Variation, Parkinson Disease, Point Mutation.
- Adolescent, Adult, Aged, Aged, 80 and over, Diagnosis, Differential, Female, Genotype, Humans, Male, Middle Aged.
Abstract
Mutations in LRRK2 were first reported as causing Parkinson's disease (PD) in late 2004. Since then, approximately a dozen LRRK2 substitutions have been identified that are believed to be pathogenic mutations. The substitution of adenine for guanine at nucleotide 4541 (4541G>A) in LRRK2 was recently reported. This substitution resulted in the replacement of an arginine at position 1514 with a glutamine (R1514Q). Although this substitution was not found in a large cohort of controls, its pathogenicity could not be verified. We have now genotyped the R1514Q substitution in a sample of 954 PD patients from 429 multiplex PD families. This substitution was identified in 1.8% of the PD patients; however, the majority of the PD sibships segregating this substitution were discordant for this putative mutation. In addition, the R1514Q substitution was detected in 1.4% of neurologically evaluated, control individuals. These data suggest that the R1514Q variant is not a pathogenic LRRK2 mutation. We believe it is imperative that the causative nature of any newly identified genetic variant be determined before it is included in any panel for diagnostic testing.
DOI: 10.1002/mds.21233
PubMed: 17149721
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation.</title><author><name sortKey="Nichols, William C" sort="Nichols, William C" uniqKey="Nichols W" first="William C" last="Nichols">William C. Nichols</name><affiliation wicri:level="1"><nlm:affiliation>Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. bill.nichols@cchmc.org</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229</wicri:regionArea><wicri:noRegion>Ohio 45229</wicri:noRegion></affiliation></author><author><name sortKey="Marek, Diane K" sort="Marek, Diane K" uniqKey="Marek D" first="Diane K" last="Marek">Diane K. Marek</name></author><author><name sortKey="Pauciulo, Michael W" sort="Pauciulo, Michael W" uniqKey="Pauciulo M" first="Michael W" last="Pauciulo">Michael W. Pauciulo</name></author><author><name sortKey="Pankratz, Nathan" sort="Pankratz, Nathan" uniqKey="Pankratz N" first="Nathan" last="Pankratz">Nathan Pankratz</name></author><author><name sortKey="Halter, Cheryl A" sort="Halter, Cheryl A" uniqKey="Halter C" first="Cheryl A" last="Halter">Cheryl A. Halter</name></author><author><name sortKey="Rudolph, Alice" sort="Rudolph, Alice" uniqKey="Rudolph A" first="Alice" last="Rudolph">Alice Rudolph</name></author><author><name sortKey="Shults, Clifford W" sort="Shults, Clifford W" uniqKey="Shults C" first="Clifford W" last="Shults">Clifford W. Shults</name></author><author><name sortKey="Wojcieszek, Joanne" sort="Wojcieszek, Joanne" uniqKey="Wojcieszek J" first="Joanne" last="Wojcieszek">Joanne Wojcieszek</name></author><author><name sortKey="Foroud, Tatiana" sort="Foroud, Tatiana" uniqKey="Foroud T" first="Tatiana" last="Foroud">Tatiana Foroud</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2007">2007</date><idno type="doi">10.1002/mds.21233</idno><idno type="RBID">pubmed:17149721</idno><idno type="pmid">17149721</idno><idno type="wicri:Area/PubMed/Corpus">002946</idno><idno type="wicri:Area/PubMed/Curation">002946</idno><idno type="wicri:Area/PubMed/Checkpoint">002604</idno><idno type="wicri:Area/Ncbi/Merge">001993</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation.</title><author><name sortKey="Nichols, William C" sort="Nichols, William C" uniqKey="Nichols W" first="William C" last="Nichols">William C. Nichols</name><affiliation wicri:level="1"><nlm:affiliation>Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. bill.nichols@cchmc.org</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229</wicri:regionArea><wicri:noRegion>Ohio 45229</wicri:noRegion></affiliation></author><author><name sortKey="Marek, Diane K" sort="Marek, Diane K" uniqKey="Marek D" first="Diane K" last="Marek">Diane K. Marek</name></author><author><name sortKey="Pauciulo, Michael W" sort="Pauciulo, Michael W" uniqKey="Pauciulo M" first="Michael W" last="Pauciulo">Michael W. Pauciulo</name></author><author><name sortKey="Pankratz, Nathan" sort="Pankratz, Nathan" uniqKey="Pankratz N" first="Nathan" last="Pankratz">Nathan Pankratz</name></author><author><name sortKey="Halter, Cheryl A" sort="Halter, Cheryl A" uniqKey="Halter C" first="Cheryl A" last="Halter">Cheryl A. Halter</name></author><author><name sortKey="Rudolph, Alice" sort="Rudolph, Alice" uniqKey="Rudolph A" first="Alice" last="Rudolph">Alice Rudolph</name></author><author><name sortKey="Shults, Clifford W" sort="Shults, Clifford W" uniqKey="Shults C" first="Clifford W" last="Shults">Clifford W. Shults</name></author><author><name sortKey="Wojcieszek, Joanne" sort="Wojcieszek, Joanne" uniqKey="Wojcieszek J" first="Joanne" last="Wojcieszek">Joanne Wojcieszek</name></author><author><name sortKey="Foroud, Tatiana" sort="Foroud, Tatiana" uniqKey="Foroud T" first="Tatiana" last="Foroud">Tatiana Foroud</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="ISSN">0885-3185</idno><imprint><date when="2007" type="published">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenine Nucleotide Translocator 1 (genetics)</term><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Amino Acid Substitution (genetics)</term><term>Arginine (genetics)</term><term>Carrier Proteins (genetics)</term><term>Diagnosis, Differential</term><term>Female</term><term>Genetic Variation (genetics)</term><term>Genotype</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Parkinson Disease (diagnosis)</term><term>Parkinson Disease (genetics)</term><term>Point Mutation (genetics)</term><term>Protein-Serine-Threonine Kinases (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Adenine Nucleotide Translocator 1</term><term>Arginine</term><term>Carrier Proteins</term><term>Protein-Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Amino Acid Substitution</term><term>Genetic Variation</term><term>Parkinson Disease</term><term>Point Mutation</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Diagnosis, Differential</term><term>Female</term><term>Genotype</term><term>Humans</term><term>Male</term><term>Middle Aged</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mutations in LRRK2 were first reported as causing Parkinson's disease (PD) in late 2004. Since then, approximately a dozen LRRK2 substitutions have been identified that are believed to be pathogenic mutations. The substitution of adenine for guanine at nucleotide 4541 (4541G>A) in LRRK2 was recently reported. This substitution resulted in the replacement of an arginine at position 1514 with a glutamine (R1514Q). Although this substitution was not found in a large cohort of controls, its pathogenicity could not be verified. We have now genotyped the R1514Q substitution in a sample of 954 PD patients from 429 multiplex PD families. This substitution was identified in 1.8% of the PD patients; however, the majority of the PD sibships segregating this substitution were discordant for this putative mutation. In addition, the R1514Q substitution was detected in 1.4% of neurologically evaluated, control individuals. These data suggest that the R1514Q variant is not a pathogenic LRRK2 mutation. We believe it is imperative that the causative nature of any newly identified genetic variant be determined before it is included in any panel for diagnostic testing.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">17149721</PMID><DateCreated><Year>2007</Year><Month>02</Month><Day>05</Day></DateCreated><DateCompleted><Year>2007</Year><Month>03</Month><Day>23</Day></DateCompleted><DateRevised><Year>2015</Year><Month>04</Month><Day>07</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0885-3185</ISSN><JournalIssue CitedMedium="Print"><Volume>22</Volume><Issue>2</Issue><PubDate><Year>2007</Year><Month>Jan</Month><Day>15</Day></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation.</ArticleTitle><Pagination><MedlinePgn>254-7</MedlinePgn></Pagination><Abstract><AbstractText>Mutations in LRRK2 were first reported as causing Parkinson's disease (PD) in late 2004. Since then, approximately a dozen LRRK2 substitutions have been identified that are believed to be pathogenic mutations. The substitution of adenine for guanine at nucleotide 4541 (4541G>A) in LRRK2 was recently reported. This substitution resulted in the replacement of an arginine at position 1514 with a glutamine (R1514Q). Although this substitution was not found in a large cohort of controls, its pathogenicity could not be verified. We have now genotyped the R1514Q substitution in a sample of 954 PD patients from 429 multiplex PD families. This substitution was identified in 1.8% of the PD patients; however, the majority of the PD sibships segregating this substitution were discordant for this putative mutation. In addition, the R1514Q substitution was detected in 1.4% of neurologically evaluated, control individuals. These data suggest that the R1514Q variant is not a pathogenic LRRK2 mutation. We believe it is imperative that the causative nature of any newly identified genetic variant be determined before it is included in any panel for diagnostic testing.</AbstractText><CopyrightInformation>(c) 2006 Movement Disorder Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Nichols</LastName><ForeName>William C</ForeName><Initials>WC</Initials><AffiliationInfo><Affiliation>Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. bill.nichols@cchmc.org</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marek</LastName><ForeName>Diane K</ForeName><Initials>DK</Initials></Author><Author ValidYN="Y"><LastName>Pauciulo</LastName><ForeName>Michael W</ForeName><Initials>MW</Initials></Author><Author ValidYN="Y"><LastName>Pankratz</LastName><ForeName>Nathan</ForeName><Initials>N</Initials></Author><Author ValidYN="Y"><LastName>Halter</LastName><ForeName>Cheryl A</ForeName><Initials>CA</Initials></Author><Author ValidYN="Y"><LastName>Rudolph</LastName><ForeName>Alice</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Shults</LastName><ForeName>Clifford W</ForeName><Initials>CW</Initials></Author><Author ValidYN="Y"><LastName>Wojcieszek</LastName><ForeName>Joanne</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Foroud</LastName><ForeName>Tatiana</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><CollectiveName>Parkinson Study Group - PROGENI Investigators</CollectiveName></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 NS37167</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U24 AG021886</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U24 AG021886</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mov Disord</MedlineTA><NlmUniqueID>8610688</NlmUniqueID><ISSNLinking>0885-3185</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D033741">Adenine Nucleotide Translocator 1</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002352">Carrier Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C037853">glutamine transport proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>94ZLA3W45F</RegistryNumber><NameOfSubstance UI="D001120">Arginine</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="C495280">LRRK2 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D017346">Protein-Serine-Threonine Kinases</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N" UI="D033741">Adenine Nucleotide Translocator 1</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000293">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000328">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000368">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000369">Aged, 80 and over</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D019943">Amino Acid Substitution</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D001120">Arginine</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D002352">Carrier Proteins</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D003937">Diagnosis, Differential</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005260">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D014644">Genetic Variation</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="Y" UI="D005838">Genotype</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006801">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008297">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008875">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D010300">Parkinson Disease</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000175">diagnosis</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D017354">Point Mutation</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D017346">Protein-Serine-Threonine Kinases</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2006</Year><Month>12</Month><Day>7</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2007</Year><Month>3</Month><Day>24</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2006</Year><Month>12</Month><Day>7</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="doi">10.1002/mds.21233</ArticleId><ArticleId IdType="pubmed">17149721</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country></list><tree><noCountry><name sortKey="Foroud, Tatiana" sort="Foroud, Tatiana" uniqKey="Foroud T" first="Tatiana" last="Foroud">Tatiana Foroud</name><name sortKey="Halter, Cheryl A" sort="Halter, Cheryl A" uniqKey="Halter C" first="Cheryl A" last="Halter">Cheryl A. Halter</name><name sortKey="Marek, Diane K" sort="Marek, Diane K" uniqKey="Marek D" first="Diane K" last="Marek">Diane K. Marek</name><name sortKey="Pankratz, Nathan" sort="Pankratz, Nathan" uniqKey="Pankratz N" first="Nathan" last="Pankratz">Nathan Pankratz</name><name sortKey="Pauciulo, Michael W" sort="Pauciulo, Michael W" uniqKey="Pauciulo M" first="Michael W" last="Pauciulo">Michael W. Pauciulo</name><name sortKey="Rudolph, Alice" sort="Rudolph, Alice" uniqKey="Rudolph A" first="Alice" last="Rudolph">Alice Rudolph</name><name sortKey="Shults, Clifford W" sort="Shults, Clifford W" uniqKey="Shults C" first="Clifford W" last="Shults">Clifford W. Shults</name><name sortKey="Wojcieszek, Joanne" sort="Wojcieszek, Joanne" uniqKey="Wojcieszek J" first="Joanne" last="Wojcieszek">Joanne Wojcieszek</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Nichols, William C" sort="Nichols, William C" uniqKey="Nichols W" first="William C" last="Nichols">William C. 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