{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T16:42:30Z","timestamp":1775839350482,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T00:00:00Z","timestamp":1683072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The phospholipase A2 group VI gene (<jats:italic>PLA2G6<\/jats:italic>) encodes an enzyme that catalyzes the hydrolytic release of fatty acids from phospholipids. Four neurological disorders with infantile, juvenile, or early adult\u2010onset are associated with <jats:italic>PLA2G6<\/jats:italic> genetic alterations, namely infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (ANAD), dystonia\u2010parkinsonism (DP), and autosomal recessive early\u2010onset parkinsonism (AREP). Few studies in Africa reported <jats:italic>PLA2G6<\/jats:italic>\u2010associated disorders and none with parkinsonism of late adult onset.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>The patients were clinically assessed following UK Brain Bank diagnostic criteria and International Parkinson and Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS\u2010UPDRS). Brain MRI without contrast was performed. Genetic testing was done using a custom\u2010made Twist panel, screening 34 known genes, 27 risk factors, and 8 candidate genes associated with parkinsonism. Filtered variants were PCR\u2010amplified and validated using Sanger sequencing and also tested in additional family members to study their segregation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>Two siblings born to consanguineous parents developed parkinsonism at the age of 58 and 60\u2009years, respectively. MRI showed an enlarged right hippocampus in patient 2, but no overt abnormalities indicative of INAD or iron deposits. We found two heterozygous variants in <jats:italic>PLA2G6<\/jats:italic>, an in\u2010frame deletion NM_003560:c.2070_2072del (p.Val691del) and a missense variant NM_003560:c.956C&gt;T (p.Thr319Met). Both variants were classified as pathogenic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first case in which <jats:italic>PLA2G6<\/jats:italic> is associated with late\u2010onset parkinsonism. Functional analysis is needed to confirm the dual effect of both variants on the structure and function of iPLA2\u03b2.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51781","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T06:05:43Z","timestamp":1683180343000},"page":"983-989","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp><i>PLA2G6<\/i><\/scp>\u2010associated late\u2010onset parkinsonism in a Sudanese family"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3669-7367","authenticated-orcid":false,"given":"Yousuf","family":"Bakhit","sequence":"first","affiliation":[{"name":"Department of Neurology University Hospital Bonn  Bonn Germany"},{"name":"Department of Basic Medical Sciences, Faculty of Dentistry University of Khartoum  Khartoum Sudan"},{"name":"Sudan Neuroscience Projects University of Khartoum  Khartoum Sudan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christelle","family":"Tesson","sequence":"additional","affiliation":[{"name":"Assistance Publique H\u00f4pitaux de Paris, Department of Neurology, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital Sorbonne Universit\u00e9, Paris Brain Institute \u2013 ICM, Inserm, CNRS  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed O.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Sudan Neuroscience Projects University of Khartoum  Khartoum Sudan"},{"name":"Department of Biochemistry, Faculty of Medicine Sudan University of Science and Technology  Khartoum Sudan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khalid","family":"Eltom","sequence":"additional","affiliation":[{"name":"Sudan Neuroscience Projects University of Khartoum  Khartoum Sudan"},{"name":"Department of Medical Cell Biology, Uppsala Biomedical Center Uppsala University  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isra","family":"Eltazi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Soba Teaching Hospital, And Department of Medicine, Faculty of Medicine University of Khartoum  Khartoum Sudan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liena E.O.","family":"Elsayed","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, College of Medicine Princess Nourah bint Abdulrahman University  Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne","family":"Lesage","sequence":"additional","affiliation":[{"name":"Assistance Publique H\u00f4pitaux de Paris, Department of Neurology, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital Sorbonne Universit\u00e9, Paris Brain Institute \u2013 ICM, Inserm, CNRS  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osheik","family":"Seidi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Soba Teaching Hospital, And Department of Medicine, Faculty of Medicine University of Khartoum  Khartoum Sudan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Christophe","family":"Corvol","sequence":"additional","affiliation":[{"name":"Assistance Publique H\u00f4pitaux de Paris, Department of Neurology, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital Sorbonne Universit\u00e9, Paris Brain Institute \u2013 ICM, Inserm, CNRS  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ullrich","family":"W\u00fcllner","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Bonn  Bonn Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE)  Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Sudanese Parkinson's Disease Study Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,5,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432\u20101327.1999.00418.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.05.019"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.10.6.1763"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.15.8642"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600\u20100854.2000.010608.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010642\u201047449\u20101_3"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/2051\u20105960\u20101\u201012"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23971"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u2010444\u201063233\u20103.00019\u20101"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2010.05.009"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.7916\/D84Q7T4W"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23221"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318221acd3"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.7916\/D81G0M12"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28807"},{"key":"e_1_2_10_17_1","first-page":"165","article-title":"Parkinson's disease society brain Bank, London: overview and research","volume":"39","author":"Daniel SE","year":"1993","journal-title":"J Neural Transm Suppl"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22340"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.06.006"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3943"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks596"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00299-001-0399-7"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1086\/508572"},{"issue":"1","key":"e_1_2_10_26_1","first-page":"1","article-title":"\u57fa\u56e0\u7684\u6539\u53d8NIH public access","volume":"23","author":"Kuang G","year":"2014","journal-title":"Bone"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881\u2010018\u20100592\u2010y"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.01.003"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000515"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2017.01.005"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51781","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T08:10:46Z","timestamp":1692432646000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.51781"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,3]]},"references-count":29,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/acn3.51781"],"URL":"https:\/\/doi.org\/10.1002\/acn3.51781","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,3]]},"assertion":[{"value":"2022-11-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}