T313M PINK1 mutation in an extended highly consanguineous saudi family with early-onset parkinson disease
Identifieur interne : 002900 ( Main/Exploration ); précédent : 002899; suivant : 002901T313M PINK1 mutation in an extended highly consanguineous saudi family with early-onset parkinson disease
Auteurs : Muhammad A. Chishti [Arabie saoudite] ; Saeed Bohlega [Arabie saoudite] ; Maqbool Ahmed [Arabie saoudite] ; Arslan Loualich [Arabie saoudite] ; Pamela Carroll [Arabie saoudite] ; Christine Sato [Canada] ; Peter St George-Hyslop [Canada] ; David Westaway [Canada] ; Ekaterina Rogaeva [Canada]Source :
- Archives of neurology : (Chicago) [ 0003-9942 ] ; 2006.
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- Pascal (Inist)
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Abstract
Background: To date, 5 well-confirmed genes for Parkinson disease (PD) have been identified, including 3 autosomal recessive genes: PTEN-induced putative kinase 1 (PINK1), parkin, and Dj-1. Almost nothing is known about the genetics of PD in Saudi Arabia; however, consanguineous families, not infrequent in this population, could be important in the evaluation of known PD genes and the search for new PD factors in the future. Objective: To investigate known recessive PD genes in 5 consanguineous Saudi families with PD. Design: The entire open frame as well as the untranslated region and all 5' and 3' intron-exon boundaries of the PINK1, parkin, and DJ-1 genes were sequenced in 5 probands in Saudi families. Results: Four of 5 probands tested negative for PINK1, parkin, and DJ-1 mutations. However, in a large Saudi family with PD with at least 3 consanguineous marriages between first cousins, we detected a threonine to methionine substitution at codon 313 (T313M) PINK1 mutation that affected the kinase domain. Manifestations of the disease in this family included early onset (age, 28-38 years), tremulous movement, slow progression, diurnal fluctuations, bradykinesia, good response to levodopa therapy, and only mild dyskinesias. A neurologist blinded to genetic status clinically evaluated 15 family members, all older than 20 years, and diagnosed PD only in individuals who were later found to be homozygous for the T313M mutation. None of the 13 heterozygotes demonstrated any sign of PD. Conclusion: A homozygous T313M mutation is responsible for PD in this large Saudi family. However, the heterozygous T313M mutation does not act as a PD susceptibility factor, which is in contrast to several reports of mutations affecting only 1 PINK1 allele discovered in sporadic PD.
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A" sort="Chishti, Muhammad A" uniqKey="Chishti M" first="Muhammad A." last="Chishti">Muhammad A. Chishti</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Comparative Medicine, King Faisal Specialist Hospital and Research Center</s1><s2>Riyadh</s2><s3>SAU</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Arabie saoudite</country><wicri:noRegion>Riyadh</wicri:noRegion></affiliation></author><author><name sortKey="Bohlega, Saeed" sort="Bohlega, Saeed" uniqKey="Bohlega S" first="Saeed" last="Bohlega">Saeed Bohlega</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Neuroscience, King Faisal Specialist Hospital and Research Center</s1><s2>Riyadh</s2><s3>SAU</s3><sZ>2 aut.</sZ></inist:fA14><country>Arabie saoudite</country><wicri:noRegion>Riyadh</wicri:noRegion></affiliation></author><author><name sortKey="Ahmed, Maqbool" sort="Ahmed, Maqbool" uniqKey="Ahmed M" first="Maqbool" last="Ahmed">Maqbool Ahmed</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Comparative Medicine, King Faisal Specialist Hospital and Research Center</s1><s2>Riyadh</s2><s3>SAU</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Arabie saoudite</country><wicri:noRegion>Riyadh</wicri:noRegion></affiliation></author><author><name sortKey="Loualich, Arslan" sort="Loualich, Arslan" uniqKey="Loualich A" first="Arslan" last="Loualich">Arslan Loualich</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Comparative Medicine, King Faisal Specialist Hospital and Research Center</s1><s2>Riyadh</s2><s3>SAU</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Arabie saoudite</country><wicri:noRegion>Riyadh</wicri:noRegion></affiliation></author><author><name sortKey="Carroll, Pamela" sort="Carroll, Pamela" uniqKey="Carroll P" first="Pamela" last="Carroll">Pamela Carroll</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Aragene Laboratory, King Faisal Specialist Hospital and Research Center</s1><s2>Riyadh</s2><s3>SAU</s3><sZ>5 aut.</sZ></inist:fA14><country>Arabie saoudite</country><wicri:noRegion>Riyadh</wicri:noRegion></affiliation></author><author><name sortKey="Sato, Christine" sort="Sato, Christine" uniqKey="Sato C" first="Christine" last="Sato">Christine Sato</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="St George Hyslop, Peter" sort="St George Hyslop, Peter" uniqKey="St George Hyslop P" first="Peter" last="St George-Hyslop">Peter St George-Hyslop</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Toronto Western Hospital Research Institute, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Westaway, David" sort="Westaway, David" uniqKey="Westaway D" first="David" last="Westaway">David Westaway</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Rogaeva, Ekaterina" sort="Rogaeva, Ekaterina" uniqKey="Rogaeva E" first="Ekaterina" last="Rogaeva">Ekaterina Rogaeva</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author></analytic><series><title level="j" type="main">Archives of neurology : (Chicago)</title><title level="j" type="abbreviated">Arch. neurol. : (Chic.)</title><idno type="ISSN">0003-9942</idno><imprint><date when="2006">2006</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Archives of neurology : (Chicago)</title><title level="j" type="abbreviated">Arch. neurol. : (Chic.)</title><idno type="ISSN">0003-9942</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Mutation</term><term>Nervous system diseases</term><term>Parkinson disease</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Système nerveux pathologie</term><term>Parkinson maladie</term><term>Mutation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background: To date, 5 well-confirmed genes for Parkinson disease (PD) have been identified, including 3 autosomal recessive genes: PTEN-induced putative kinase 1 (PINK1), parkin, and Dj-1. Almost nothing is known about the genetics of PD in Saudi Arabia; however, consanguineous families, not infrequent in this population, could be important in the evaluation of known PD genes and the search for new PD factors in the future. Objective: To investigate known recessive PD genes in 5 consanguineous Saudi families with PD. Design: The entire open frame as well as the untranslated region and all 5' and 3' intron-exon boundaries of the PINK1, parkin, and DJ-1 genes were sequenced in 5 probands in Saudi families. Results: Four of 5 probands tested negative for PINK1, parkin, and DJ-1 mutations. However, in a large Saudi family with PD with at least 3 consanguineous marriages between first cousins, we detected a threonine to methionine substitution at codon 313 (T313M) PINK1 mutation that affected the kinase domain. Manifestations of the disease in this family included early onset (age, 28-38 years), tremulous movement, slow progression, diurnal fluctuations, bradykinesia, good response to levodopa therapy, and only mild dyskinesias. A neurologist blinded to genetic status clinically evaluated 15 family members, all older than 20 years, and diagnosed PD only in individuals who were later found to be homozygous for the T313M mutation. None of the 13 heterozygotes demonstrated any sign of PD. Conclusion: A homozygous T313M mutation is responsible for PD in this large Saudi family. However, the heterozygous T313M mutation does not act as a PD susceptibility factor, which is in contrast to several reports of mutations affecting only 1 PINK1 allele discovered in sporadic PD.</div></front></TEI><affiliations><list><country><li>Arabie saoudite</li><li>Canada</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Arabie saoudite"><noRegion><name sortKey="Chishti, Muhammad A" sort="Chishti, Muhammad A" uniqKey="Chishti M" first="Muhammad A." last="Chishti">Muhammad A. Chishti</name></noRegion><name sortKey="Ahmed, Maqbool" sort="Ahmed, Maqbool" uniqKey="Ahmed M" first="Maqbool" last="Ahmed">Maqbool Ahmed</name><name sortKey="Bohlega, Saeed" sort="Bohlega, Saeed" uniqKey="Bohlega S" first="Saeed" last="Bohlega">Saeed Bohlega</name><name sortKey="Carroll, Pamela" sort="Carroll, Pamela" uniqKey="Carroll P" first="Pamela" last="Carroll">Pamela Carroll</name><name sortKey="Loualich, Arslan" sort="Loualich, Arslan" uniqKey="Loualich A" first="Arslan" last="Loualich">Arslan Loualich</name></country><country name="Canada"><region name="Ontario"><name sortKey="Sato, Christine" sort="Sato, Christine" uniqKey="Sato C" first="Christine" last="Sato">Christine Sato</name></region><name sortKey="Rogaeva, Ekaterina" sort="Rogaeva, Ekaterina" uniqKey="Rogaeva E" first="Ekaterina" last="Rogaeva">Ekaterina Rogaeva</name><name sortKey="St George Hyslop, Peter" sort="St George Hyslop, Peter" uniqKey="St George Hyslop P" first="Peter" last="St George-Hyslop">Peter St George-Hyslop</name><name sortKey="St George Hyslop, Peter" sort="St George Hyslop, Peter" uniqKey="St George Hyslop P" first="Peter" last="St George-Hyslop">Peter St George-Hyslop</name><name sortKey="Westaway, David" sort="Westaway, David" uniqKey="Westaway D" first="David" last="Westaway">David Westaway</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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