Have a personal or library account? Click to login
Decoding the Alphabet Soup: A Practical Guide to Genetic Testing in Hyperkinetic Movement Disorders Cover

Decoding the Alphabet Soup: A Practical Guide to Genetic Testing in Hyperkinetic Movement Disorders

Open Access
|Jun 2025

References

  1. 1Pös O, Radvanszky J, Buglyó G, Pös Z, Rusnakova D, Nagy B, et al. DNA copy number variation: Main characteristics, evolutionary significance, and pathological aspects. Biomed J. 2021 Oct;44(5):54859. DOI: 10.1016/j.bj.2021.02.003
  2. 2Alkan C, Coe BP, Eichler EE. Genome structural variation discovery and genotyping. Nat Rev Genet. 2011 May;12(5):36376. DOI: 10.1038/nrg2958
  3. 3Riggs ER, Andersen EF, Cherry AM, Kantarci S, Kearney H, Patel A, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):24557. DOI: 10.1038/s41436-019-0686-8
  4. 4den Dunnen JT, Dalgleish R, Maglott DR, Hart RK, Greenblatt MS, McGowan-Jordan J, et al. HGVS Recommendations for the Description of Sequence Variants: 2016 Update. Hum Mutat. 2016 Jun;37(6):5649. DOI: 10.1002/humu.22981
  5. 5Margulies M, Egholm M, Altman WE, Attiya S, Bader JS, Bemben LA, et al. Genome sequencing in microfabricated high-density picolitre reactors. Nature. 2005 Sep 15;437(7057):37680.
  6. 6Pehlivan D, Beck CR, Okamoto Y, Harel T, Akdemir ZHC, Jhangiani SN, et al. The role of combined SNV and CNV burden in patients with distal symmetric polyneuropathy. Genet Med. 2016 May;18(5):44351. DOI: 10.1038/gim.2015.124
  7. 7Wallace SE, Bean LJH. Educational Materials — Genetic Testing: Current Approaches. 2017 Mar 14 [Updated 2020 Jun 18.
  8. 8Orr HT, Chung MY, Banfi S, Kwiatkowski TJ, Servadio A, Beaudet AL, et al. Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat Genet. 1993 Jul;4(3):2216. DOI: 10.1038/ng0793-221
  9. 9Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, et al. CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet. 1994 Nov;8(3):2218. DOI: 10.1038/ng1194-221
  10. 10Hsieh M, Lin SJ, Chen JF, Lin HM, Hsiao KM, Li SY, et al. Identification of the spinocerebellar ataxia type 7 mutation in Taiwan: application of PCR-based Southern blot. J Neurol. 2000 Aug;247(8):6239. DOI: 10.1007/s004150070131
  11. 11van der Veen S, Zutt R, Klein C, Marras C, Berkovic SF, Caviness JN, et al. Nomenclature of Genetically Determined Myoclonus Syndromes: Recommendations of the International Parkinson and Movement Disorder Society Task Force. Mov Disord. 2019 Nov;34(11):160213. DOI: 10.1002/mds.27828
  12. 12Rossi M, Anheim M, Durr A, Klein C, Koenig M, Synofzik M, et al. The genetic nomenclature of recessive cerebellar ataxias. Mov Disord. 2018 Jul;33(7):105676. DOI: 10.1002/mds.27415
  13. 13Gusella JF, Wexler NS, Conneally PM, Naylor SL, Anderson MA, Tanzi RE, et al. A polymorphic DNA marker genetically linked to Huntington’s disease. Nature. 1983 Nov 17;306(5940):2348. DOI: 10.1038/306234a0
  14. 14A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. The Huntington’s Disease Collaborative Research Group. Cell. 1993 Mar 26;72(6):97183. DOI: 10.1016/0092-8674(93)90585-E
  15. 15Bates GP, Dorsey R, Gusella JF, Hayden MR, Kay C, Leavitt BR, et al. Huntington disease. Nat Rev Dis Primers. 2015 Apr 23;1:15005. DOI: 10.1038/nrdp.2015.5
  16. 16Hensman Moss DJ, Poulter M, Beck J, Hehir J, Polke JM, Campbell T, et al. C9orf72 expansions are the most common genetic cause of Huntington disease phenocopies. Neurology. 2014 Jan 28;82(4):2929. DOI: 10.1212/WNL.0000000000000061
  17. 17Mead S. Prion disease genetics. Eur J Hum Genet. 2006 Mar;14(3):27381. DOI: 10.1038/sj.ejhg.5201544
  18. 18Todd PK, Paulson HL. RNA-mediated neurodegeneration in repeat expansion disorders. Ann Neurol. 2010 Mar;67(3):291300. DOI: 10.1002/ana.21948
  19. 19Kambouris M, Bohlega S, Al-Tahan A, Meyer BF. Localization of the gene for a novel autosomal recessive neurodegenerative Huntington-like disorder to 4p15.3. Am J Hum Genet. 2000 Feb;66(2):44552. DOI: 10.1086/302744
  20. 20Magri S, Nanetti L, Gellera C, Sarto E, Rizzo E, Mongelli A, et al. Digenic inheritance of STUB1 variants and TBP polyglutamine expansions explains the incomplete penetrance of SCA17 and SCA48. Genet Med. 2022 Jan;24(1):2940. DOI: 10.1016/j.gim.2021.08.003
  21. 21Burke JR, Wingfield MS, Lewis KE, Roses AD, Lee JE, Hulette C, et al. The Haw River syndrome: dentatorubropallidoluysian atrophy (DRPLA) in an African-American family. Nat Genet. 1994 Aug;7(4):5214. DOI: 10.1038/ng0894-521
  22. 22Becher MW, Rubinsztein DC, Leggo J, Wagster MV, Stine OC, Ranen NG, et al. Dentatorubral and pallidoluysian atrophy (DRPLA). Clinical and neuropathological findings in genetically confirmed North American and European pedigrees. Mov Disord. 1997 Jul;12(4):51930. DOI: 10.1002/mds.870120408
  23. 23Grimaldi S, Cupidi C, Smirne N, Bernardi L, Giacalone F, Piccione G, et al. The largest caucasian kindred with dentatorubral-pallidoluysian atrophy: A founder mutation in italy. Mov Disord. 2019 Dec;34(12):191924. DOI: 10.1002/mds.27879
  24. 24Prades S, de Gusmao CM, Grimaldi S, Shiloh-Malawsky Y, Felton T, Houlden H. DRPLA. 1999 Aug 6 [Updated 2023 Sep 21]. In: GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 19932024. Margaret P Adam, Jerry Feldman, Ghayda M Mirzaa, Roberta A Pagon, Stephanie E Wallace, Anne Amemiya; Available from: https://www.ncbi.nlm.nih.gov/books/NBK1491/
  25. 25Danek A, Rubio JP, Rampoldi L, Ho M, Dobson-Stone C, Tison F, et al. McLeod neuroacanthocytosis: genotype and phenotype. Ann Neurol. 2001 Dec;50(6):75564. DOI: 10.1002/ana.10035
  26. 26Peikert K, Dobson-Stone C, Rampoldi L, Miltenberger-Miltenyi G, Neiman A, De Camilli P, et al. VPS13A Disease. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993 [cited 2025 Jun 15]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1387/
  27. 27Breedveld GJ, van Dongen JWF, Danesino C, Guala A, Percy AK, Dure LS, et al. Mutations in TITF-1 are associated with benign hereditary chorea. Hum Mol Genet. 2002 Apr 15;11(8):9719. DOI: 10.1093/hmg/11.8.971
  28. 28Kleiner-Fisman G, Rogaeva E, Halliday W, Houle S, Kawarai T, Sato C, et al. Benign hereditary chorea: clinical, genetic, and pathological findings. Ann Neurol. 2003 Aug;54(2):2447. DOI: 10.1002/ana.10637
  29. 29Konishi T, Kono S, Fujimoto M, Terada T, Matsushita K, Ouchi Y, et al. Benign hereditary chorea: dopaminergic brain imaging in patients with a novel intronic NKX2.1 gene mutation. J Neurol. 2013 Jan;260(1):20713. DOI: 10.1007/s00415-012-6618-z
  30. 30Mencacci NE, Kamsteeg EJ, Nakashima K, R’Bibo L, Lynch DS, Balint B, et al. De Novo Mutations in PDE10A Cause Childhood-Onset Chorea with Bilateral Striatal Lesions. Am J Hum Genet. 2016 Apr 7;98(4):76371. DOI: 10.1016/j.ajhg.2016.02.015
  31. 31Diggle CP, Sukoff Rizzo SJ, Popiolek M, Hinttala R, Schülke JP, Kurian MA, et al. Biallelic Mutations in PDE10A Lead to Loss of Striatal PDE10A and a Hyperkinetic Movement Disorder with Onset in Infancy. Am J Hum Genet. 2016 Apr 7;98(4):73543. DOI: 10.1016/j.ajhg.2016.03.015
  32. 32Feng H, Sjögren B, Karaj B, Shaw V, Gezer A, Neubig RR. Movement disorder in GNAO1 encephalopathy associated with gain-of-function mutations. Neurology. 2017 Aug 22;89(8):76270. DOI: 10.1212/WNL.0000000000004262
  33. 33Opal P, Tintner R, Jankovic J, Leung J, Breakefield XO, Friedman J, et al. Intrafamilial phenotypic variability of the DYT1 dystonia: from asymptomatic TOR1A gene carrier status to dystonic storm. Mov Disord. 2002 Mar;17(2):33945. DOI: 10.1002/mds.10096
  34. 34Kamm C, Fischer H, Garavaglia B, Kullmann S, Sharma M, Schrader C, et al. Susceptibility to DYT1 dystonia in European patients is modified by the D216H polymorphism. Neurology. 2008 Jun 3;70(23):22612. DOI: 10.1212/01.wnl.0000313838.05734.8a
  35. 35Charlesworth G, Bhatia KP, Wood NW. The genetics of dystonia: new twists in an old tale. Brain. 2013 Jul;136(Pt 7):201737. DOI: 10.1093/brain/awt138
  36. 36Meyer E, Carss KJ, Rankin J, Nichols JME, Grozeva D, Joseph AP, et al. Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia. Nat Genet. 2017 Feb;49(2):22337.
  37. 37Ichinose H, Ohye T, Takahashi E, Seki N, Hori T, Segawa M, et al. Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene. Nat Genet. 1994 Nov;8(3):23642. DOI: 10.1038/ng1194-236
  38. 38Hirano M, Imaiso Y, Ueno S. Differential splicing of the GTP cyclohydrolase I RNA in dopa-responsive dystonia. Biochem Biophys Res Commun. 1997 May 19;234(2):3169. DOI: 10.1006/bbrc.1997.6632
  39. 39Domingo A, Lee LV, Brüggemann N, Freimann K, Kaiser FJ, Jamora RDG, et al. Woman with x-linked recessive dystonia-parkinsonism: clue to the epidemiology of parkinsonism in Filipino women? JAMA Neurol. 2014 Sep;71(9):117780. DOI: 10.1001/jamaneurol.2014.56
  40. 40Aneichyk T, Hendriks WT, Yadav R, Shin D, Gao D, Vaine CA, et al. Dissecting the Causal Mechanism of X-Linked Dystonia-Parkinsonism by Integrating Genome and Transcriptome Assembly. Cell. 2018 Feb 22;172(5):897909.e21. DOI: 10.1016/j.cell.2018.02.011
  41. 41Gianfrancesco O, Geary B, Savage AL, Billingsley KJ, Bubb VJ, Quinn JP. The Role of SINE-VNTR-Alu (SVA) Retrotransposons in Shaping the Human Genome. Int J Mol Sci. 2019 Nov 27;20(23):5977. DOI: 10.3390/ijms20235977
  42. 42De Gregorio L, Jinnah HA, Harris JC, Nyhan WL, Schretlen DJ, Trombley LM, et al. Lesch-Nyhan disease in a female with a clinically normal monozygotic twin. Molecular genetics and metabolism [Internet]. 2005 May [cited 2024 Oct 6];85(1). Available from: https://pubmed.ncbi.nlm.nih.gov/15862283/. DOI: 10.1016/j.ymgme.2004.11.009
  43. 43Zech M, Kumar KR, Reining S, Reunert J, Tchan M, Riley LG, et al. Biallelic AOPEP Loss-of-Function Variants Cause Progressive Dystonia with Prominent Limb Involvement. Mov Disord. 2022 Jan;37(1):13747. DOI: 10.1002/mds.28804
  44. 44Steel D, Zech M, Zhao C, Barwick KES, Burke D, Demailly D, et al. Loss-of-Function Variants in HOPS Complex Genes VPS16 and VPS41 Cause Early Onset Dystonia Associated with Lysosomal Abnormalities. Ann Neurol. 2020 Nov;88(5):86777. DOI: 10.1002/ana.25879
  45. 45Musacchio T, Zech M, Reich MM, Winkelmann J, Volkmann J. A Recurrent EIF2AK2 Missense Variant Causes Autosomal-Dominant Isolated Dystonia. Ann Neurol. 2021 Jun;89(6):12578. DOI: 10.1002/ana.26081
  46. 46Coarelli G, Wirth T, Tranchant C, Koenig M, Durr A, Anheim M. The inherited cerebellar ataxias: an update. J Neurol. 2023 Jan;270(1):20822. DOI: 10.1007/s00415-022-11383-6
  47. 47Gardiner SL, Boogaard MW, Trompet S, de Mutsert R, Rosendaal FR, Gussekloo J, et al. Prevalence of Carriers of Intermediate and Pathological Polyglutamine Disease-Associated Alleles Among Large Population-Based Cohorts. JAMA Neurol. 2019 Jun 1;76(6):6506. DOI: 10.1001/jamaneurol.2019.0423
  48. 48Scott SS de O, Pedroso JL, Barsottini OGP, França-Junior MC, Braga-Neto P. Natural history and epidemiology of the spinocerebellar ataxias: Insights from the first description to nowadays. J Neurol Sci. 2020 Oct 15;417:117082. DOI: 10.1016/j.jns.2020.117082
  49. 49Martins S, Sequeiros J. Origins and Spread of Machado-Joseph Disease Ancestral Mutations Events. Adv Exp Med Biol. 2018;1049:24354. DOI: 10.1007/978-3-319-71779-1_12
  50. 50Kraus-Perrotta C, Lagalwar S. Expansion, mosaicism and interruption: mechanisms of the CAG repeat mutation in spinocerebellar ataxia type 1. Cerebellum Ataxias. 2016;3:20. DOI: 10.1186/s40673-016-0058-y
  51. 51Menon RP, Nethisinghe S, Faggiano S, Vannocci T, Rezaei H, Pemble S, et al. The role of interruptions in polyQ in the pathology of SCA1. PLoS Genet. 2013;9(7):e1003648. DOI: 10.1371/journal.pgen.1003648
  52. 52Ramos A, Raposo M, Milà M, Bettencourt C, Houlden H, Cisneros B, et al. Verification of Inter-laboratorial Genotyping Consistency in the Molecular Diagnosis of Polyglutamine Spinocerebellar Ataxias. J Mol Neurosci. 2016 Jan;58(1):837. DOI: 10.1007/s12031-015-0646-y
  53. 53Tan D, Wei C, Chen Z, Huang Y, Deng J, Li J, et al. CAG Repeat Expansion in THAP11 Is Associated with a Novel Spinocerebellar Ataxia. Mov Disord. 2023 Jul;38(7):128293. DOI: 10.1002/mds.29412
  54. 54Berciano J, Infante J, García A, Polo JM, Volpini V, Combarros O. Very late-onset Friedreich’s ataxia with minimal GAA1 expansion mimicking multiple system atrophy of cerebellar type. Mov Disord. 2005 Dec;20(12):16435. DOI: 10.1002/mds.20644
  55. 55Dominik N, Magri S, Currò R, Abati E, Facchini S, Corbetta M, et al. Normal and pathogenic variation of RFC1 repeat expansions: implications for clinical diagnosis. Brain. 2023 Dec 1;146(12):50609.
  56. 56Pellerin D, Danzi MC, Wilke C, Renaud M, Fazal S, Dicaire MJ, et al. Deep Intronic FGF14 GAA Repeat Expansion in Late-Onset Cerebellar Ataxia. N Engl J Med. 2023 Jan 12;388(2):12841. DOI: 10.1016/j.jns.2023.121139
  57. 57Cortese A, Tozza S, Yau WY, Rossi S, Beecroft SJ, Jaunmuktane Z, et al. Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion. Brain. 2020 Feb 1;143(2):48090. DOI: 10.1093/brain/awz418
  58. 58Assenza G, Benvenga A, Gennaro E, Tombini M, Campana C, Assenza F, et al. A novel c132–134del mutation in Unverricht-Lundborg disease and the review of literature of heterozygous compound patients. Epilepsia. 2017 Feb;58(2):e315. DOI: 10.1111/epi.13626
  59. 59Canafoglia L, Gennaro E, Capovilla G, Gobbi G, Boni A, Beccaria F, et al. Electroclinical presentation and genotype-phenotype relationships in patients with Unverricht-Lundborg disease carrying compound heterozygous CSTB point and indel mutations. Epilepsia. 2012 Dec;53(12):21207. DOI: 10.1111/j.1528-1167.2012.03718.x
  60. 60Koskenkorva P, Hyppönen J, Aikiä M, Mervaala E, Kiviranta T, Eriksson K, et al. Severer phenotype in Unverricht-Lundborg disease (EPM1) patients compound heterozygous for the dodecamer repeat expansion and the c.202C>T mutation in the CSTB gene. Neurodegener Dis. 2011;8(6):51522. DOI: 10.1159/000323470
  61. 61Mancini GMS, Schot R, de Wit MCY, de Coo RF, Oostenbrink R, Bindels-de Heus K, et al. CSTB null mutation associated with microcephaly, early developmental delay, and severe dyskinesia. Neurology. 2016 Mar 1;86(9):8778. DOI: 10.1212/WNL.0000000000002422
  62. 62O’Brien A, Marshall CR, Blaser S, Ray PN, Yoon G. Severe neurodegeneration, progressive cerebral volume loss and diffuse hypomyelination associated with a homozygous frameshift mutation in CSTB. Eur J Hum Genet. 2017 Jun;25(6):7758. DOI: 10.1038/ejhg.2017.39
  63. 63Grabowski M, Zimprich A, Lorenz-Depiereux B, Kalscheuer V, Asmus F, Gasser T, et al. The epsilon-sarcoglycan gene (SGCE), mutated in myoclonus-dystonia syndrome, is maternally imprinted. Eur J Hum Genet. 2003 Feb;11(2):13844. DOI: 10.1038/sj.ejhg.5200938
  64. 64Carecchio M, Magliozzi M, Copetti M, Ferraris A, Bernardini L, Bonetti M, et al. Defining the epsilon-sarcoglycan (SGCE) gene phenotypic signature in myoclonus-dystonia: a reappraisal of genetic testing criteria. Mov Disord. 2013 Jun;28(6):78794. DOI: 10.1002/mds.25506
  65. 65Guettard E, Portnoi MF, Lohmann-Hedrich K, Keren B, Rossignol S, Winkler S, et al. Myoclonus-dystonia due to maternal uniparental disomy. Arch Neurol. 2008 Oct;65(10):13805. DOI: 10.1001/archneur.65.10.1380
  66. 66Williams L, Waller SE, Bradley M, Lockhart A, Narayanan RK, Kumar KR, et al. ATP1A3 related disease manifesting as rapid onset dystonia-parkinsonism with prominent myoclonus and exaggerated startle. Parkinsonism Relat Disord. 2023 Dec;117:105864. DOI: 10.1016/j.parkreldis.2023.105864
  67. 67Behera S, Catreux S, Rossi M, Truong S, Huang Z, Ruehle M, et al. Comprehensive and accurate genome analysis at scale using DRAGEN accelerated algorithms. bioRxiv. 2024 Jan 6;2024.01.02.573821. DOI: 10.1101/2024.01.02.573821
  68. 68Leija-Salazar M, Sedlazeck FJ, Toffoli M, Mullin S, Mokretar K, Athanasopoulou M, et al. Evaluation of the detection of GBA missense mutations and other variants using the Oxford Nanopore MinION. Mol Genet Genomic Med. 2019 Mar;7(3):e564. DOI: 10.1002/mgg3.564
  69. 69Toffoli M, Chen X, Sedlazeck FJ, Lee CY, Mullin S, Higgins A, et al. Comprehensive short and long read sequencing analysis for the Gaucher and Parkinson’s disease-associated GBA gene. Commun Biol. 2022 Jul 6;5(1):670. DOI: 10.1038/s42003-022-03610-7
  70. 70Nicastro N, Ranza E, Antonarakis SE, Horvath J. Pure Progressive Ataxia and Palatal Tremor (PAPT) Associated with a New Polymerase Gamma (POLG) Mutation. Cerebellum. 2016 Dec;15(6):82931. DOI: 10.1007/s12311-015-0749-6
  71. 71Samuel M, Torun N, Tuite PJ, Sharpe JA, Lang AE. Progressive ataxia and palatal tremor (PAPT): clinical and MRI assessment with review of palatal tremors. Brain. 2004 Jun;127(Pt 6):125268. DOI: 10.1093/brain/awh137
  72. 72Knight MA, Gardner RJM, Bahlo M, Matsuura T, Dixon JA, Forrest SM, et al. Dominantly inherited ataxia and dysphonia with dentate calcification: spinocerebellar ataxia type 20. Brain. 2004 May;127(Pt 5):117281. DOI: 10.1093/brain/awh139
  73. 73Pretegiani E, Rosini F, Federighi P, Cerase A, Dotti MT, Rufa A. Pendular nystagmus, palatal tremor and progressive ataxia in GM2-gangliosidosis. Eur J Neurol. 2015 Jun;22(6):e6769. DOI: 10.1111/ene.12661
  74. 74Hayflick SJ, Kurian MA, Hogarth P. Neurodegeneration with brain iron accumulation. Handb Clin Neurol. 2018;147:293305. DOI: 10.1016/B978-0-444-63233-3.00019-1
  75. 75Knight MA, Hernandez D, Diede SJ, Dauwerse HG, Rafferty I, van de Leemput J, et al. A duplication at chromosome 11q12.2–11q12.3 is associated with spinocerebellar ataxia type 20. Hum Mol Genet. 2008 Dec 15;17(24):384753. DOI: 10.1093/hmg/ddn283
  76. 76Corbett MA, Depienne C, Veneziano L, Klein KM, Brancati F, Guerrini R, et al. Genetics of familial adult myoclonus epilepsy: From linkage studies to noncoding repeat expansions. Epilepsia. 2023 Jun;64(Suppl 1):S1421. DOI: 10.1111/epi.17610
  77. 77Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):40524. DOI: 10.1038/gim.2015.30
  78. 78Pejaver V, Byrne AB, Feng BJ, Pagel KA, Mooney SD, Karchin R, et al. Calibration of computational tools for missense variant pathogenicity classification and ClinGen recommendations for PP3/BP4 criteria. Am J Hum Genet. 2022 Dec 1;109(12):216377. DOI: 10.1016/j.ajhg.2022.10.013
  79. 79Mirza-Schreiber N, Zech M, Wilson R, Brunet T, Wagner M, Jech R, et al. Blood DNA methylation provides an accurate biomarker of KMT2B-related dystonia and predicts onset. Brain. 2022 Apr 18;145(2):64454. DOI: 10.1093/brain/awab360
  80. 80Chung MY, Ranum LP, Duvick LA, Servadio A, Zoghbi HY, Orr HT. Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type I. Nat Genet. 1993 Nov;5(3):2548. DOI: 10.1038/ng1193-254
  81. 81Nance MA. Genetic counseling and testing for Huntington’s disease: A historical review. Am J Med Genet B Neuropsychiatr Genet. 2017 Jan;174(1):7592. DOI: 10.1002/ajmg.b.32453
  82. 82Pinto E Vairo F, Kemppainen JL, Vitek CRR, Whalen DA, Kolbert KJ, Sikkink KJ, et al. Implementation of genomic medicine for rare disease in a tertiary healthcare system: Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD). J Transl Med. 2023 Jun 23;21(1):410. DOI: 10.1186/s12967-023-04183-7
  83. 83Curic E, Ewans L, Pysar R, Taylan F, Botto LD, Nordgren A, et al. International Undiagnosed Diseases Programs (UDPs): components and outcomes. Orphanet J Rare Dis. 2023 Nov 9;18(1):348. DOI: 10.1186/s13023-023-02966-1
  84. 84Montano C, Cassini T, Ziegler SG, Boehm M, Nicoli ER, Mindell JA, et al. Diagnosis and discovery: Insights from the NIH Undiagnosed Diseases Program. J Inherit Metab Dis. 2022 Sep;45(5):90718. DOI: 10.1002/jimd.12506
  85. 85Gatto EM, Walker RH, Gonzalez C, Cesarini M, Cossu G, Stephen CD, et al. Worldwide barriers to genetic testing for movement disorders. Eur J Neurol. 2021 Jun;28(6):19019. DOI: 10.1111/ene.14826
  86. 86Audet S, Triassi V, Gelinas M, Legault-Cadieux N, Ferraro V, Duquette A, et al. Integration of multi-omics technologies for molecular diagnosis in ataxia patients. Front Genet. 2023;14:1304711. DOI: 10.3389/fgene.2023.1304711
  87. 87Zech M, Winkelmann J. Next-generation sequencing and bioinformatics in rare movement disorders. Nat Rev Neurol. 2024 Feb;20(2):11426. DOI: 10.1038/s41582-023-00909-9
  88. 88Chen Z, Tucci A, Cipriani V, Gustavsson EK, Ibañez K, Reynolds RH, et al. Functional genomics provide key insights to improve the diagnostic yield of hereditary ataxia. Brain. 2023 Jul 3;146(7):286984. DOI: 10.1093/brain/awad009
  89. 89Zech M, Dzinovic I, Skorvanek M, Harrer P, Necpal J, Kopajtich R, et al. Combined genomics and proteomics unveils elusive variants and vast aetiologic heterogeneity in dystonia. Brain. 2025 Feb 12;awaf059. DOI: 10.1093/brain/awaf059
  90. 90Ishiura H, Doi K, Mitsui J, Yoshimura J, Matsukawa MK, Fujiyama A, et al. Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy. Nat Genet. 2018 Apr;50(4):58190. DOI: 10.1038/s41588-018-0067-2
  91. 91Florian RT, Kraft F, Leitão E, Kaya S, Klebe S, Magnin E, et al. Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3. Nat Commun. 2019 Oct 29;10(1):4919.
  92. 92Fu Y, Timp W, Sedlazeck FJ. Computational analysis of DNA methylation from long-read sequencing. Nat Rev Genet. 2025 Mar 28. DOI: 10.1038/s41576-025-00822-5
  93. 93Wilke C, Pellerin D, Mengel D, Traschütz A, Danzi MC, Dicaire MJ, et al. GAA-FGF14 ataxia (SCA27B): phenotypic profile, natural history progression and 4-aminopyridine treatment response. Brain. 2023 Oct 3;146(10):414457. DOI: 10.1093/brain/awad157
  94. 94Williams LJ, Waller S, Qiu J, Innes E, Elserafy N, Procopis P, et al. DHDDS and NUS1: A Converging Pathway and Common Phenotype. Mov Disord Clin Pract. 2024 Jan;11(1):7685. DOI: 10.1002/mdc3.13920
DOI: https://doi.org/10.5334/tohm.971 | Journal eISSN: 2160-8288
Language: English
Submitted on: Nov 7, 2024
Accepted on: Jun 17, 2025
Published on: Jun 26, 2025
Published by: Ubiquity Press
In partnership with: Paradigm Publishing Services
Publication frequency: 1 issue per year

© 2025 Claudia Del Gamba, Giulietta Maria Riboldi, published by Ubiquity Press
This work is licensed under the Creative Commons Attribution 4.0 License.