دورية أكاديمية
Progressive myoclonus epilepsies-Residual unsolved cases have marked genetic heterogeneity including dolichol-dependent protein glycosylation pathway genes.
| العنوان: | Progressive myoclonus epilepsies-Residual unsolved cases have marked genetic heterogeneity including dolichol-dependent protein glycosylation pathway genes. |
|---|---|
| المؤلفون: | Courage C; Folkhälsan Research Center, Helsinki 00290, Finland; Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki 00290, Finland., Oliver KL; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg 3084, Victoria, Australia; Population Health and Immunity Division, the Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, the University of Melbourne, Melbourne, VIC 3010, Australia., Park EJ; Department of Pharmacology and Vascular Biology and Therapeutics Program, Yale University School of Medicine, 10 Amistad Street, New Haven, CT 06520, USA., Cameron JM; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg 3084, Victoria, Australia., Grabińska KA; Department of Pharmacology and Vascular Biology and Therapeutics Program, Yale University School of Medicine, 10 Amistad Street, New Haven, CT 06520, USA., Muona M; Folkhälsan Research Center, Helsinki 00290, Finland; Blueprint Genetics, Espoo 02150, Finland., Canafoglia L; Neurophysiopathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan 20133, Italy., Gambardella A; Institute of Neurology, University Magna Græcia, Catanzaro 88100, Italy., Said E; Section of Medical Genetics, Mater dei Hospital, Msida MSD2090, Malta; Department of Anatomy and Cell Biology, University of Malta, Msida MSD2090, Malta., Afawi Z; Center for Neuroscience, Ben-Gurion University of the Negev, Be'er Sheva 8410402, Israel., Baykan B; Departments of Neurology and Clinical Neurophysiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34452, Turkey., Brandt C; Epilepsy Center Bethel, Bielefeld 33617, Germany., di Bonaventura C; Department of Human Neurosciences, Sapienza University of Rome, Viale dell'Università, 30, 00185 Rome, Italy., Chew HB; Genetics Department, Kuala Lumpur Hospital, Ministry of Health Malaysia, Jalan Pahang, 50586 Kuala Lumpur, Malaysia., Criscuolo C; Department of Neuroscience, Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples 80138, Italy., Dibbens LM; Epilepsy Research Group, Australian Centre for Precision Health, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia., Castellotti B; Unit of Genetics of Neurodegenerative and Metabolic Diseases, IRCCS Istituto Neurologico Carlo Besta Milan 20133, Italy., Riguzzi P; IRCCS Istituto delle Scienze Neurologiche di Bologna, Unit of Neurology, Bellaria Hospital, Bologna 40139, Italy., Labate A; Institute of Neurology, University Magna Græcia, Catanzaro 88100, Italy., Filla A; Department of Neuroscience, Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples 80138, Italy., Giallonardo AT; Neurology Unit, Human Neurosciences Department, Sapienza University, Rome 00185, Italy., Berecki G; Ion Channels and Disease Group, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3052, Australia., Jackson CB; Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland., Joensuu T; Folkhälsan Research Center, Helsinki 00290, Finland., Damiano JA; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg 3084, Victoria, Australia., Kivity S; Epilepsy Unit, Schneider Children's Medical Center of Israel, Petah Tiqvah 4922297, Israel., Korczyn A; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 60198, Israel., Palotie A; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki 00290, Finland; Analytic and Translational Genetics Unit, Department of Medicine, Department of Neurology and Department of Psychiatry Massachusetts General Hospital, Boston, MA 02114, USA; The Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, Boston, MA 02142, USA., Striano P; Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto 'G. Gaslini,' Genova 16147, Italy., Uccellini D; Neurology - Neurophysiology Unit, ASST dei Sette Laghi, Galmarini Tradate Hospital, Tradate 21049, Italy., Giuliano L; Dipartimento 'G.F. Ingrassia,' Università degli Studi di Catania, Catania 95131, Italy., Andermann E; Neurogenetics Unit and Epilepsy Research Group, Montreal Neurological Hospital and Institute, Montreal, QC H3A 2B4, Canada; Departments of Neurology & Neurosurgery and Human Genetics, McGill University, Montreal, QC H3A 0G4, Canada., Scheffer IE; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg 3084, Victoria, Australia; Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC 3052, Australia; Department of Paediatrics, The University of Melbourne, Royal Children's Hospital, Parkville, VIC 3052, Australia; The Florey Institute, Parkville, VIC 3052, Australia., Michelucci R; IRCCS Istituto delle Scienze Neurologiche di Bologna, Unit of Neurology, Bellaria Hospital, Bologna 40139, Italy., Bahlo M; Population Health and Immunity Division, the Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, the University of Melbourne, Melbourne, VIC 3010, Australia., Franceschetti S; Neurophysiopathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan 20133, Italy., Sessa WC; Department of Pharmacology and Vascular Biology and Therapeutics Program, Yale University School of Medicine, 10 Amistad Street, New Haven, CT 06520, USA., Berkovic SF; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg 3084, Victoria, Australia. Electronic address: s.berkovic@unimelb.edu.au., Lehesjoki AE; Folkhälsan Research Center, Helsinki 00290, Finland; Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki 00290, Finland. Electronic address: anna-elina.lehesjoki@helsinki.fi. |
| المصدر: | American journal of human genetics [Am J Hum Genet] 2021 Apr 01; Vol. 108 (4), pp. 722-738. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 0370475 Publication Model: Print Cited Medium: Internet ISSN: 1537-6605 (Electronic) Linking ISSN: 00029297 NLM ISO Abbreviation: Am J Hum Genet Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2008- : [Cambridge, MA] : Cell Press Original Publication: Baltimore, American Society of Human Genetics. |
| مواضيع طبية MeSH: | Dolichols/*metabolism , Mutation/*genetics , Myoclonic Epilepsies, Progressive/*genetics, Adolescent ; Adult ; Age of Onset ; Child ; Child, Preschool ; Cohort Studies ; DNA Copy Number Variations/genetics ; Female ; Glycosylation ; Humans ; Introns/genetics ; Male ; Middle Aged ; Myoclonic Epilepsies, Progressive/classification ; Exome Sequencing ; Young Adult |
| مستخلص: | Progressive myoclonus epilepsies (PMEs) comprise a group of clinically and genetically heterogeneous rare diseases. Over 70% of PME cases can now be molecularly solved. Known PME genes encode a variety of proteins, many involved in lysosomal and endosomal function. We performed whole-exome sequencing (WES) in 84 (78 unrelated) unsolved PME-affected individuals, with or without additional family members, to discover novel causes. We identified likely disease-causing variants in 24 out of 78 (31%) unrelated individuals, despite previous genetic analyses. The diagnostic yield was significantly higher for individuals studied as trios or families (14/28) versus singletons (10/50) (OR = 3.9, p value = 0.01, Fisher's exact test). The 24 likely solved cases of PME involved 18 genes. First, we found and functionally validated five heterozygous variants in NUS1 and DHDDS and a homozygous variant in ALG10, with no previous disease associations. All three genes are involved in dolichol-dependent protein glycosylation, a pathway not previously implicated in PME. Second, we independently validate SEMA6B as a dominant PME gene in two unrelated individuals. Third, in five families, we identified variants in established PME genes; three with intronic or copy-number changes (CLN6, GBA, NEU1) and two very rare causes (ASAH1, CERS1). Fourth, we found a group of genes usually associated with developmental and epileptic encephalopathies, but here, remarkably, presenting as PME, with or without prior developmental delay. Our systematic analysis of these cases suggests that the small residuum of unsolved cases will most likely be a collection of very rare, genetically heterogeneous etiologies. (Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.) |
| References: | Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):11567-11572. (PMID: 30348779) Biochim Biophys Acta. 2013 Nov;1832(11):1866-81. (PMID: 23402926) Am J Hum Genet. 2011 May 13;88(5):566-73. (PMID: 21549341) Epilepsy Res. 2020 Aug;164:106371. (PMID: 32485575) J Biol Chem. 2017 Oct 20;292(42):17351-17361. (PMID: 28842490) PLoS Comput Biol. 2016 Apr 21;12(4):e1004873. (PMID: 27100738) Genet Med. 2015 May;17(5):405-24. (PMID: 25741868) Autophagy. 2015;11(9):1443-57. (PMID: 26207393) Nat Neurosci. 2016 Sep;19(9):1194-6. (PMID: 27479843) Mov Disord. 2012 Mar;27(3):400-5. (PMID: 22223122) Genome Res. 2017 Nov;27(11):1895-1903. (PMID: 28887402) Am J Hum Genet. 2017 Mar 2;100(3):406-413. (PMID: 28190455) Epilepsia. 2009 May;50 Suppl 5:29-36. (PMID: 19469843) Proc Natl Acad Sci U S A. 2020 Aug 25;117(34):20794-20802. (PMID: 32817466) Genome Biol. 2016 Jun 06;17(1):122. (PMID: 27268795) Nat Commun. 2017 Aug 9;8(1):236. (PMID: 28794409) Neurology. 2014 Feb 4;82(5):405-11. (PMID: 24384641) Nature. 2020 May;581(7809):434-443. (PMID: 32461654) Neurology. 2014 Jun 3;82(22):2003-6. (PMID: 24808020) Am J Hum Genet. 2017 Nov 2;101(5):664-685. (PMID: 29100083) Ann Clin Transl Neurol. 2019 Jul;6(7):1263-1272. (PMID: 31353855) Ann Neurol. 2014 Aug;76(2):206-12. (PMID: 24782409) Cell Metab. 2014 Sep 2;20(3):448-57. (PMID: 25066056) Nucleic Acids Res. 2012 Jul;40(Web Server issue):W452-7. (PMID: 22689647) J Biol Chem. 2016 Aug 26;291(35):18582-90. (PMID: 27402831) Nat Genet. 2018 Apr;50(4):581-590. (PMID: 29507423) N Engl J Med. 2004 Nov 4;351(19):1972-7. (PMID: 15525722) EMBO J. 2011 May 13;30(12):2490-500. (PMID: 21572394) Am J Hum Genet. 2020 Apr 2;106(4):549-558. (PMID: 32169168) Ann Neurol. 1986 Mar;19(3):270-4. (PMID: 3963771) Brain Dev. 2020 Oct;42(9):696-699. (PMID: 32654954) BMC Bioinformatics. 2012 Jun 18;13:134. (PMID: 22708584) BMC Neurol. 2019 Oct 27;19(1):253. (PMID: 31656175) Am J Hum Genet. 2018 Dec 6;103(6):858-873. (PMID: 30503517) Glycobiology. 2010 Dec;20(12):1585-93. (PMID: 20685834) Nat Commun. 2019 Oct 29;10(1):4920. (PMID: 31664034) Cell Metab. 2009 Sep;10(3):208-18. (PMID: 19723497) Am J Hum Genet. 2006 Jul;79(1):62-6. (PMID: 16773566) Nucleic Acids Res. 2019 Jan 8;47(D1):D886-D894. (PMID: 30371827) Brain. 2019 Nov 1;142(11):3360-3366. (PMID: 31539032) J Biol Chem. 2012 May 25;287(22):18210-7. (PMID: 22496445) Trends Genet. 2018 Jun;34(6):466-476. (PMID: 29606283) Nat Methods. 2010 Apr;7(4):248-9. (PMID: 20354512) Nat Genet. 2015 Jan;47(1):39-46. (PMID: 25401298) Nat Commun. 2019 Oct 29;10(1):4919. (PMID: 31664039) Pediatr Res. 2003 Mar;53(3):387-95. (PMID: 12595585) Nucleic Acids Res. 2009 May;37(9):e67. (PMID: 19339519) Hum Genet. 2017 Sep;136(9):1093-1111. (PMID: 28497172) J Lipid Res. 2006 Feb;47(2):284-301. (PMID: 16288097) Seizure. 2019 Feb;65:106-108. (PMID: 30660924) Curr Opin Struct Biol. 2009 Oct;19(5):534-42. (PMID: 19801188) Am J Hum Genet. 2012 Jul 13;91(1):5-14. (PMID: 22703880) Neurology. 1983 Jan;33(1):103-6. (PMID: 6681549) Am J Hum Genet. 2011 Feb 11;88(2):201-6. (PMID: 21295283) Nat Commun. 2020 Oct 19;11(1):5273. (PMID: 33077723) Neurology. 2016 Jul 5;87(1):77-85. (PMID: 27281533) Orphanet J Rare Dis. 2016 Jun 24;11(1):84. (PMID: 27343064) N Engl J Med. 1986 Jul 31;315(5):296-305. (PMID: 3088452) Ann Neurol. 2017 May;81(5):677-689. (PMID: 28380698) Glycobiology. 1998 May;8(5):455-62. (PMID: 9597543) Elife. 2018 Oct 12;7:. (PMID: 30311906) Brain. 2013 Apr;136(Pt 4):1146-54. (PMID: 23449775) J Biol Chem. 2007 Feb 23;282(8):5506-13. (PMID: 17189275) |
| معلومات مُعتمدة: | R35 HL139945 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: dolichol-dependent glycosylation; epilepsy genetics; progressive myoclonus epilepsy; whole-exome sequencing |
| المشرفين على المادة: | 0 (Dolichols) |
| تواريخ الأحداث: | Date Created: 20210402 Date Completed: 20210507 Latest Revision: 20221207 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC8059372 |
| DOI: | 10.1016/j.ajhg.2021.03.013 |
| PMID: | 33798445 |
| قاعدة البيانات: | MEDLINE |
كن أول من يترك تعليقا!