Intracellular trafficking involves an intricate machinery of motor complexes, including the dynein complex, to shuttle cargo for autophagolysosomal degradation. Deficiency in dynein axonemal chains, as well as cytoplasmic light and intermediate chains, have been linked with ciliary dyskinesia and skeletal dysplasia. The cytoplasmic dynein 1 heavy chain protein (DYNC1H1) serves as a core complex for retrograde trafficking in neuronal axons. Dominant pathogenic variants in DYNC1H1 have been previously implicated in peripheral neuromuscular disorders (NMD) and neurodevelopmental disorders (NDD). As heavy-chain dynein is ubiquitously expressed, the apparent selectivity of heavy chain dyneinopathy for motor neuronal phenotypes remains currently unaccounted for. Here, we aimed to evaluate the full DYNC1H1-related clinical, molecular and imaging spectrum, including multisystem features and novel phenotypes presenting throughout life. We identified 47 cases from 43 families with pathogenic heterozygous variants in DYNC1H1 (aged 0-59 years) and collected phenotypic data via a comprehensive standardized survey and clinical follow-up appointments. Most patients presented with divergent and previously unrecognized neurological and multisystem features, leading to significant delays in genetic testing and establishing the correct diagnosis. Neurological phenotypes include novel autonomic features, previously rarely described behavioral disorders, movement disorders and periventricular lesions. Sensory neuropathy was identified in nine patients (median age of onset 10.6 years), of which five were only diagnosed after the second decade of life, and three had a progressive age-dependent sensory neuropathy. Novel multisystem features included primary immunodeficiency, bilateral sensorineural hearing loss, organ anomalies and skeletal manifestations, resembling the phenotypic spectrum of other dyneinopathies. We also identified an age-dependent biphasic disease course with developmental regression in the first decade and, following a period of stability, neurodegenerative progression after the second decade of life. Of note, we observed several cases in whom neurodegeneration appeared to be prompted by intercurrent systemic infections with double-stranded DNA viruses (Herpesviridae) or single-stranded RNA viruses (Ross River fever, SARS-CoV-2). Moreover, the disease course appeared to be exacerbated by viral infections regardless of age and/or severity of neurodevelopmental disorder manifestations, indicating a role of dynein in anti-viral immunity and neuronal health. In summary, our findings expand the clinical, imaging and molecular spectrum of pathogenic DYNC1H1 variants beyond motor neuropathy disorders and suggest a life-long continuum and age-related progression due to deficient intracellular trafficking. This study will facilitate early diagnosis and improve counselling and health surveillance of affected patients.

Akron Children's Hospital Genetic Center Akron OH 44308 USA

Berlin University of Applied Sciences and Technology 10587 Berlin Germany

Center for Cardiovascular Genetics Boston Children's Hospital Boston MA 02115 USA

Center for Chronically Sick Children Charité Universitätsmedizin Berlin 13353 Berlin Germany

Center for Individualized Medicine Mayo Clinic Rochester MN 55901 USA

Center for Mendelian Genomics Broad Institute Harvard Cambridge MA 02142 USA

Center for Rare Diseases Faculty of Medicine University Hospital Cologne University of Cologne 50937 Cologne Germany

Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases 50931 Cologne Germany

Department of Biology and Medical Genetics 2nd Faculty of Medicine Charles University Prague and Motol University Hospital Full Member of the ERN EpiCARE 150 06 Prague Czech Republic

Department of Clinical Genetics Cambridge University Hospitals NHS Trust Cambridge CB2 3EH UK

Department of Clinical Genetics Copenhagen University Hospital Rigshospitalet 2100 Copenhagen Denmark

Department of Clinical Genetics Maastricht University Medical Center 6229 HX Maastricht The Netherlands

Department of Genetics Cruces University Hospital Biobizkaia Health Research Institute Barakaldo 48903 Spain

Department of Medical Genetics Université Côte D'Azur Centre Hospitalier Universitaire Nice 06000 Nice France

Department of Medical Genetics University Hospital of Bordeaux 33076 Bordeaux France

Department of Neurology Maastricht University Medical Center 6229 HX Maastricht The Netherlands

Department of Neurology Rosamund Stone Zander Translational Neuroscience Center Boston Children's Hospital Boston MA 02115 USA

Department of Neuropediatrics Medical Faculty Carl Gustav Carus Technische Universität Dresden 01307 Dresden Germany

Department of Neurosciences Rehabilitation Ophthalmology Genetics Maternal and Child Health University of Genoa 16147 Genoa Italy

Department of Paediatric Neurology Neuromuscular Service Evelina Children's Hospital Guy's and St Thomas' NHS Foundation Trust London SE1 7EH UK

Department of Paediatrics Otto von Guericke University Magdeburg 39120 Magdeburg Germany

Department of Pathology Donders Institute for Brain Cognition and Behaviour Radboud University Medical Center 6525 GA Nijmegen The Netherlands

Department of Pediatric Neurology 2nd Faculty of Medicine Charles University Prague and Motol University Hospital Full Member of the ERN EpiCARE 150 06 Prague Czech Republic

Department of Pediatric Neurology Charité Universitätsmedizin Berlin 13353 Berlin Germany

Department of Pediatrics Faculty of Medicine University Hospital Cologne University of Cologne 50937 Cologne Germany

Department of Pediatrics Pediatric Neurology and Metabolic Medicine unit Kasr Al Ainy School of Medicine Cairo University 4390330 Cairo Egypt

Departments of Clinical Genomics and Neurology Mayo Clinic Rochester MN 55905 USA

Division of Genetics and Genomics Manton Center for Orphan Disease Research Boston Children's Hospital Harvard Medical School Boston MA 02445 USA

Division of Neurology Nemours Children's Health Wilmington Delaware 19803 USA

Genetic Department Pitié Salpêtrière Hospital AP HP Sorbonne University 75013 Paris France

Genetics Department AP HP Robert Debré University Hospital 75019 Paris France

Genetics Department Nantes University CHU de Nantes 44000 Nantes France

Heidelberg University Medical Faculty Heidelberg University Hospital Heidelberg Center for Pediatrics and Adolescent Medicine Department of Pediatrics 1 Division of Child Neurology and Metabolic Medicine 69120 Heidelberg Germany

Institute for Cell Biology and Neurobiology Charité Universitätsmedizin Berlin 13353 Berlin Germany

Max Planck Institute for Biology of Ageing 50931 Cologne Germany

Neurogenetic Laboratory Department of Pediatric Neurology 2nd Faculty of Medicine Charles University Prague and Motol University Hospital Full Member of the ERN EpiCARE 150 06 Prague Czech Republic

Neuromuscular and Neurogenetic Disorders of Childhood Section National Institute of Neurological Disorders and Stroke Neurogenetics Branch National Institutes of Health Bethesda MD 20892 USA

Pediatric Neurology and Muscular Diseases Unit IRCCS Giannina Gaslini Institute 16147 Genoa Italy

Radboud University Medical Center 6525 GA Nijmegen The Netherlands

Randall Centre for Cell and Molecular Biophysics Muscle Signalling Section Faculty of Life Sciences and Medicine King's College London London SE1 1YR UK

Reference Center for Malformations and Congenital Diseases of the Cerebellum and Intellectual Disabilities of Rare Causes Department of Genetics and Medical Embryology Sorbonne University Trousseau Hospital Paris 75012 Paris France

Service de pédiatrie CHU de Nantes 44000 Nantes France

The Department of Neurology Donders Institute for Brain Cognition and Behaviour Radboud University Medical Centre 6525 Nijmegen The Netherlands

U O C Genetica Medica IRCCS Istituto Giannina Gaslini 16147 Genoa Italy

See more in PubMed

Hoang  HT, Schlager  MA, Carter  AP, Bullock  SL. DYNC1H1 mutations associated with neurological diseases compromise processivity of dynein-dynactin-cargo adaptor complexes. Proc Natl Acad Sci U S A. 2017;114:E1597–E1606. PubMed PMC

Reck-Peterson  SL, Redwine  WB, Vale  RD, Carter  AP. The cytoplasmic dynein transport machinery and its many cargoes. Nat Rev Mol Cell Biol. 2018;19:382–398. PubMed PMC

Hirokawa  N, Niwa  S, Tanaka  Y. Molecular motors in neurons: Transport mechanisms and roles in brain function, development, and disease. Neuron. 2010;68:610–638. PubMed

Schiavo  G, Greensmith  L, Hafezparast  M, Fisher  EMC. Cytoplasmic dynein heavy chain: The servant of many masters. Trends Neurosci. 2013;36:641–651. PubMed PMC

Marzo  MG, Griswold  JM, Ruff  KM, Buchmeier  RE, Fees  CP, Markus  SM. Molecular basis for dyneinopathies reveals insight into dynein regulation and dysfunction. Elife. 2019;8:e47246. PubMed PMC

Li  JT, Dong  SQ, Zhu  DQ, et al.  Expanding the phenotypic and genetic spectrum of neuromuscular diseases caused by DYNC1H1 mutations. Front Neurol. 2022;13:943324. PubMed PMC

Strickland A  V, Schabhüttl  M, Offenbacher  H, et al.  Mutation screen reveals novel variants and expands the phenotypes associated with DYNC1H1. J Neurol. 2015;262:2124–2134. PubMed PMC

Weedon  MN, Hastings  R, Caswell  R, et al.  Exome sequencing identifies a DYNC1H1 mutation in a large pedigree with dominant axonal Charcot-Marie-Tooth disease. Am J Hum Genet. 2011;89:308–312. PubMed PMC

Poirier  K, Lebrun  N, Broix  L, et al.  Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly. Nat Genet. 2013;45:639–647. PubMed PMC

Harms  MB, Allred  P, Gardner  R, et al.  Dominant spinal muscular atrophy with lower extremity predominance: Linkage to 14q32. Neurology. 2010;75:539–546. PubMed PMC

Harms  MB, Ori-McKenney  KM, Scoto  M, et al.  Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy. Neurology. 2012;78:1714–1720. PubMed PMC

Becker  LL, Dafsari  HS, Schallner  J, et al.  The clinical-phenotype continuum in DYNC1H1-related disorders—Genomic profiling and proposal for a novel classification. J Hum Genet. 2020;65:1003–1017. PubMed PMC

Amabile  S, Jeffries  L, McGrath  JM, et al.  DYNC1H1-related disorders: A description of four new unrelated patients and a comprehensive review of previously reported variants. Am J Med Genet A. 2020;182:2049–2057. PubMed

Willemsen  MH, Vissers  LEL, Willemsen  MAAP, et al.  Mutations in DYNC1H1 cause severe intellectual disability with neuronal migration defects. J Med Genet. 2012;49:179–183. PubMed

Dafsari  HS, Becker  L, von der Hagen  M, Cirak  S. Genomic profiling in neuronal dyneinopathies and updated classifications. Am J Med Genet A. 2021;185:2607–2610. PubMed

Sobreira  N, Schiettecatte  F, Valle  D, Hamosh  A. GeneMatcher: A matching tool for connecting investigators with an interest in the same gene. Hum Mutat. 2015;36:928–930. PubMed PMC

Kopanos  C, Tsiolkas  V, Kouris  A, et al.  VarSome: The human genomic variant search engine. Bioinformatics. 2019;35:1978–1980. PubMed PMC

Chopra  M, Savatt  JM, Bingaman  TI, et al.  Clinical variants paired with phenotype: A rich resource for brain gene curation. Genet Med. 2024;26:101035. PubMed PMC

Körner  RW, Bansemir  OY, Franke  R, Sturm  J, Dafsari  HS. Atopy and elevation of IgE, IgG3, and IgG4 may be risk factors for post COVID-19 condition in children and adolescents. Children (Basel). 2023;10:1598. PubMed PMC

Hentrich  L, Parnes  M, Lotze  TE, et al.  Novel genetic and phenotypic expansion in GOSR2-related progressive myoclonus epilepsy. Genes (Basel). 2023;14:1860. PubMed PMC

Dafsari  HS, Kawalia  A, Sprute  R, et al.  Novel mutations in SLC6A5 with benign course in hyperekplexia. Cold Spring Harb Mol Case Stud. 2019;5:a004465. PubMed PMC

Allen  NM, Dafsari  HS, Wraige  E, Jungbluth  H. Neck-tongue syndrome: An underrecognized childhood onset cephalalgia. J Child Neurol. 2018;33:347–350. PubMed

Robinson  PN, Köhler  S, Bauer  S, Seelow  D, Horn  D, Mundlos  S. The human phenotype ontology: A tool for annotating and analyzing human hereditary disease. Am J Hum Genet. 2008;83:610–615. PubMed PMC

Köhler  S, Gargano  M, Matentzoglu  N, et al.  The human phenotype ontology in 2021. Nucleic Acids Res. 2021;49(D1):D1207–D1217. PubMed PMC

Saffari  A, Lau  T, Tajsharghi  H, et al.  The clinical and genetic spectrum of autosomal-recessive TOR1A -related disorders. Brain. 2023;146:3273–3288. PubMed PMC

Beecroft  SJ, McLean  CA, Delatycki  MB, et al.  Expanding the phenotypic spectrum associated with mutations of DYNC1H1. Neuromuscul Disord.  2017;27:607–615. PubMed

Niu  Q, Wang  X, Shi  M, Jin  Q. A novel DYNC1H1 mutation causing spinal muscular atrophy with lower extremity predominance. Neurol Genet. 2015;1:e20. PubMed PMC

Ding  D, Chen  Z, Li  K, et al.  Identification of a de novo DYNC1H1 mutation via WES according to published guidelines. Sci Rep. 2016;6:20423. PubMed PMC

Lin  Z, Liu  Z, Li  X, et al.  Whole-exome sequencing identifies a novel de novo mutation in DYNC1H1 in epileptic encephalopathies. Sci Rep. 2017;7:258. PubMed PMC

Chan  SHS, van Alfen  N, Thuestad  IJ, et al.  A recurrent de novo DYNC1H1 tail domain mutation causes spinal muscular atrophy with lower extremity predominance, learning difficulties and mild brain abnormality. Neuromuscul Disord.  2018;28:750–756. PubMed

Gelineau-Morel  R, Lukacs  M, Weaver  KN, Hufnagel  RB, Gilbert  DL, Stottmann  RW. Congenital cataracts and gut dysmotility in a DYNC1H1 dyneinopathy patient. Genes (Basel). 2016;7:85. PubMed PMC

Chen  Y, Xu  Y, Li  G, et al.  Exome sequencing identifies de novo DYNC1H1 mutations associated with distal spinal muscular atrophy and malformations of cortical development. J Child Neurol. 2017;32:379–386. PubMed

Laquerriere  A, Maillard  C, Cavallin  M, et al.  Neuropathological hallmarks of brain malformations in extreme phenotypes related to DYNC1H1 mutations. J Neuropathol Exp Neurol. 2017;76:195–205. PubMed

Hertecant  J, Komara  M, Nagi  A, Suleiman  J, Al-Gazali  L, Ali  BR. A novel de novo mutation in DYNC1H1 gene underlying malformation of cortical development and cataract. Meta Gene. 2016;9:124–127. PubMed PMC

Peeters  K, Bervoets  S, Chamova  T, et al.  Novel mutations in the DYNC1H1 tail domain refine the genetic and clinical spectrum of dyneinopathies. Hum Mutat. 2015;36:287–291. PubMed

Tsurusaki  Y, Saitoh  S, Tomizawa  K, et al.  A DYNC1H1 mutation causes a dominant spinal muscular atrophy with lower extremity predominance. Neurogenetics. 2012;13:327–332. PubMed

Das  J, Lilleker  JB, Jabbal  K, Ealing  J. A missense mutation in DYNC1H1 gene causing spinal muscular atrophy—Lower extremity, dominant. Neurol Neurochir Pol. 2018;52:293–297. PubMed

Punetha  J, Monges  S, Franchi  ME, Hoffman  EP, Cirak  S, Tesi-Rocha  C. Exome sequencing identifies DYNC1H1 variant associated with vertebral abnormality and spinal muscular atrophy with lower extremity predominance. Pediatr Neurol. 2015;52:239–244. PubMed PMC

Zillhardt  JL, Poirier  K, Broix  L, et al.  Mosaic parental germline mutations causing recurrent forms of malformations of cortical development. Eur J Hum Genet.  2016;24:611–614. PubMed PMC

Fiorillo  C, Moro  F, Yi  J, et al.  Novel dynein DYNC1H1 neck and motor domain mutations link distal spinal muscular atrophy and abnormal cortical development. Hum Mutat. 2014;35:298–302. PubMed PMC

Scoto  M, Rossor  AM, Harms  MB, et al.  Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy. Neurology. 2015;84:668–679. PubMed PMC

Jamuar  SS, Lam  ATN, Kircher  M, et al.  Somatic mutations in cerebral cortical malformations. N Engl J Med.  2014;371:733–743. PubMed PMC

Möller  B, Coppolla  A, Jungbluth  H, Dafsari  HS. DYNC1H1-Related Disorders. GeneReviews® [Internet]. Published online 14 March 2024. Accessed 28 March 2024. https://www.ncbi.nlm.nih.gov/books/NBK601997/

Rodrigues  CHM, Pires  DEV, Ascher  DB. DynaMut2: Assessing changes in stability and flexibility upon single and multiple point missense mutations. Protein Sci. 2021;30:60–69. PubMed PMC

Camilleri  M. Gastrointestinal motility disorders in neurologic disease. Journal of Clinical Investigation. 2021;131:e143771. PubMed PMC

Kim  H, Jung  HR, Kim  JB, Kim  DJ. Autonomic dysfunction in sleep disorders: From neurobiological basis to potential therapeutic approaches. J Clin Neurol. 2022;18:140–151. PubMed PMC

Petry-Schmelzer  JN, Krause  M, Dembek  TA, et al.  Non-motor outcomes depend on location of neurostimulation in Parkinson’s disease. Brain. 2019;142:3592–3604. PubMed

Goldstein  AM, Thapar  N, Karunaratne  TB, De Giorgio  R. Clinical aspects of neurointestinal disease: Pathophysiology, diagnosis, and treatment. Dev Biol. 2016;417:217–228. PubMed

De Giorgio  R, Bianco  F, Latorre  R, Caio  G, Clavenzani  P, Bonora  E. Enteric neuropathies: Yesterday, today and tomorrow. Adv Exp Med Biol. 2016;891:123–133. PubMed

Di Nardo  G, Blandizzi  C, Volta  U, et al.  Review article: Molecular, pathological and therapeutic features of human enteric neuropathies. Aliment Pharmacol Ther. 2008;28:25–42. PubMed

Cullup  T, Kho  AL, Dionisi-Vici  C, et al.  Recessive mutations in EPG5 cause vici syndrome, a multisystem disorder with defective autophagy. Nat Genet. 2013;45:83–87. PubMed PMC

Esteve  C, Francescatto  L, Tan  PL, et al.  Loss-of-function mutations in UNC45A cause a syndrome associating cholestasis, diarrhea, impaired hearing, and bone fragility. Am J Hum Genet. 2018;102:364–374. PubMed PMC

Wells  R, Tonkin  A. Clinical approach to autonomic dysfunction. Intern Med J. 2016;46:1134–1139. PubMed

Goldberger  JJ, Arora  R, Buckley  U, Shivkumar  K. Autonomic nervous system dysfunction: JACC focus seminar. J Am Coll Cardiol. 2019;73:1189–1206. PubMed PMC

Dineen  J, Freeman  R. Autonomic neuropathy. Semin Neurol. 2015;35:458–468. PubMed

Sánchez-Manso  JC, Gujarathi  R, Varacallo  M. Autonomic Dysfunction. StatPearls. Published online 24 October 2022. Accessed 28 March 2023. https://www.ncbi.nlm.nih.gov/books/NBK430888/

Matanis  T, Akhmanova  A, Wulf  P, et al.  Bicaudal-D regulates COPI-independent Golgi–ER transport by recruiting the dynein–dynactin motor complex. Nat Cell Biol.  2002;4:986–992. PubMed

Shomron  O, Hirschberg  K, Burakov  A, et al.  Positioning of endoplasmic reticulum exit sites around the Golgi depends on BicaudalD2 and Rab6 activity. Traffic. 2021;22:64–77. PubMed

Brault  J, Bardin  S, Lampic  M, et al.  RAB6 and dynein drive post-Golgi apical transport to prevent neuronal progenitor delamination. EMBO Rep. 2022;23:e54605. PubMed PMC

Wassmer  T, Attar  N, Harterink  M, et al.  The retromer coat complex coordinates endosomal sorting and dynein-mediated transport, with carrier recognition by the trans-Golgi network. Dev Cell. 2009;17:110–122. PubMed PMC

Langworthy  MM, Appel  B. Schwann cell myelination requires Dynein function. Neural Dev. 2012;7:1–15. PubMed PMC

Chen  XJ, Levedakou  EN, Millen  KJ, Wollmann  RL, Soliven  B, Popko  B. Proprioceptive sensory neuropathy in mice with a mutation in the cytoplasmic dynein heavy chain 1 gene. J Neurosci.  2007;27:14515–14524. PubMed PMC

Iwaki  A, Moriwaki  K, Sobajima  T, et al.  Loss of Rab6a in the small intestine causes lipid accumulation and epithelial cell death from lactation. FASEB J. 2020;34:9450–9465. PubMed

Yang  L, Liu  G, Li  X, et al.  Small GTPase RAB6 deficiency promotes alveolar progenitor cell renewal and attenuates PM2.5-induced lung injury and fibrosis. Cell Death Dis. 2020;11:827. PubMed PMC

Dornan L  G, Simpson J  C. Rab6-mediated retrograde trafficking from the Golgi: The trouble with tubules. Small GTPases. 2023;14:26. PubMed PMC

Buser  DP, Spang  A. Protein sorting from endosomes to the TGN. Front Cell Dev Biol. 2023;11:1140605. PubMed PMC

Kuballa  P, Nolte  WM, Castoreno  AB, Xavier  RJ. Autophagy and the immune system. Annu Rev Immunol. 2012;30:611–646. PubMed

Sharma  V, Verma  S, Seranova  E, Sarkar  S, Kumar  D. Selective autophagy and Xenophagy in infection and disease. Front Cell Dev Biol. 2018;6(NOV):147. PubMed PMC

Mao  K, Klionsky  DJ. Xenophagy: A battlefield between host and microbe, and a possible avenue for cancer treatment. Autophagy. 2017;13:223. PubMed PMC

Ye  J, Zheng  M. Autophagosome trafficking. Adv Exp Med Biol. 2021;1208:67–77. PubMed

Wongchitrat  P, Chanmee  T, Govitrapong  P. Molecular mechanisms associated with neurodegeneration of neurotropic viral infection. Mol Neurobiol. 2023;61:2881–2903. PubMed PMC

Zavala-Vargas  DI, Visoso-Carbajal  G, Cedillo-Barrón  L, et al.  Interaction of the Zika virus with the cytoplasmic dynein-1. Virol J. 2023;20:43. PubMed PMC

Stoyanova  G, Jabeen  S, Landazuri Vinueza  J, Ghosh Roy  S, Lockshin  RA, Zakeri  Z. Zika virus triggers autophagy to exploit host lipid metabolism and drive viral replication. Cell Commun Signal. 2023;21:114. PubMed PMC

Hou  W, Kang  W, Li  Y, Shan  Y, Wang  S, Liu  F. Dynamic dissection of dynein and kinesin-1 cooperatively mediated intercellular transport of porcine epidemic diarrhea coronavirus along microtubule using single virus tracking. Virulence. 2021;12:615–629. PubMed PMC

Rosichini  M, Bordoni  V, Silvestris  DA, et al.  SARS-CoV-2 infection of thymus induces loss of function that correlates with disease severity. J Allergy Clin Immunol. 2023;151:911–921. PubMed PMC

Glon  D, Vilmen  G, Perdiz  D, et al.  Essential role of hyperacetylated microtubules in innate immunity escape orchestrated by the EBV-encoded BHRF1 protein. PLoS Pathog. 2022;18:e1010371. PubMed PMC

Banerjee  A, Kulkarni  S, Mukherjee  A. Herpes simplex virus: The hostile guest that takes over your home. Front Microbiol. 2020;11:733. PubMed PMC

Döhner  K, Wolfstein  A, Prank  U, et al.  Function of dynein and dynactin in herpes simplex virus capsid transport. Mol Biol Cell. 2002;13:2795–2809. PubMed PMC

Suomalainen  M, Nakano  MY, Keller  S, Boucke  K, Stidwill  RP, Greber  UF. Microtubule-dependent plus- and minus end–directed motilities are competing processes for nuclear targeting of adenovirus. J Cell Biol. 1999;144:657–672. PubMed PMC

Bremner  KH, Scherer  J, Yi  J, Vershinin  M, Gross  SP, Vallee  RB. Article adenovirus transport via direct interaction of cytoplasmic dynein with the viral capsid hexon subunit. Cell Host Microbe.  2009;6:523–535. PubMed PMC

Wouk  J, Rechenchoski  DZ, Rodrigues  BCD, Ribelato  EV, Faccin-Galhardi  LC. Viral infections and their relationship to neurological disorders. Arch Virol. 2021;166:733–753. PubMed PMC

Bjornevik  K, Cortese  M, Healy  BC, et al.  Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science. 2022;375:296–301. PubMed

Grut  V, Biström  M, Salzer  J, et al.  Human herpesvirus 6A and axonal injury before the clinical onset of multiple sclerosis. Brain. 2024;147:177–185. PubMed PMC

Fadda  G, Yea  C, O’Mahony  J, et al.  Epstein–Barr virus strongly associates with pediatric multiple sclerosis, but not myelin oligodendrocyte glycoprotein-antibody-associated disease. Ann Neurol. 2024;95:700–705. PubMed

Vietzen  H, Berger  SM, Kühner  LM, et al.  Ineffective control of Epstein-Barr-virus-induced autoimmunity increases the risk for multiple sclerosis. Cell. 2023;186:5705–5718.e13. PubMed

Chorin  O, Hirsch  Y, Rock  R, et al.  Vici syndrome in Israel: Clinical and molecular insights. Front Genet. 2022;13:991721. PubMed PMC

Dafsari  HS, Ebrahimi-Fakhari  D, Saffari  A, Deneubourg  C, Fanto  M, Jungbluth  H. EPG5-Related Disorder. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, eds. GeneReviews®. University of Washington; 2022. PubMed

Cayre  S, Faraldo  MM, Bardin  S, Miserey-Lenkei  S, Deugnier  MA, Goud  B. RAB6 GTPase regulates mammary secretory function by controlling the activation of STAT5. Development. 2020;147:dev190744. PubMed PMC

Acres  MJ, Gothe  F, Grainger  A, et al.  Signal transducer and activator of transcription 5B deficiency due to a novel missense mutation in the coiled-coil domain. J Allergy Clin Immunol. 2019;143:413–416.e4. PubMed PMC

Kawabata  M, Matsuo  H, Koito  T, et al.  Legionella hijacks the host Golgi-to-ER retrograde pathway for the association of Legionella-containing vacuole with the ER. PLoS Pathog. 2021;17:e1009437. PubMed PMC

Knowles  MR, Daniels  LA, Davis  SD, Zariwala  MA, Leigh  MW. Primary ciliary dyskinesia. Recent advances in diagnostics, genetics, and characterization of clinical disease. Am J Respir Crit Care Med. 2013;188:913–922. PubMed PMC

O’Callaghan  C, Rutman  A, Williams  GM, Hirst  RA. Inner dynein arm defects causing primary ciliary dyskinesia: Repeat testing required. Eur Respir J.  2011;38:603–607. PubMed

Bayram  N, Kaçar Bayram  A, Daimagüler  HS, et al.  Genotype-phenotype correlations in ocular manifestations of Marinesco–Sjögren syndrome: Case report and literature review. Eur J Ophthalmol. 2022;32:NP92–NP97. PubMed

Byrne  S, Jansen  L, U-King-Im  JM, et al.  EPG5-related vici syndrome: A paradigm of neurodevelopmental disorders with defective autophagy. Brain. 2016;139:765–781. PubMed PMC

Dafsari  HS, Pemberton  JG, Ferrer  EA, et al.  PI4K2A deficiency causes innate error in intracellular trafficking with developmental and epileptic-dyskinetic encephalopathy. Ann Clin Transl Neurol. 2022;9:1345–1358. PubMed PMC

Cason  SE, Carman  PJ, Van Duyne  C, Goldsmith  J, Dominguez  R, Holzbaur  ELF. Sequential dynein effectors regulate axonal autophagosome motility in a maturation-dependent pathway. J Cell Biol. 2021;220:e202010179. PubMed PMC

Cason  SE, Holzbaur  ELF. Axonal transport of autophagosomes is regulated by dynein activators JIP3/JIP4 and ARF/RAB GTPases. J Cell Biol. 2023;222:e202301084. PubMed PMC

Yap  CC, Digilio  L, McMahon  LP, Wang  T, Winckler  B. Dynein is required for Rab7-dependent endosome maturation, retrograde dendritic transport, and degradation. J Neurosci. 2022;42:4415–4434. PubMed PMC