Skip to main content
SpringerLink
Log in

Joubert syndrome: brain and spinal cord malformations in genotyped cases and implications for neurodevelopmental functions of primary cilia

  • Original Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Joubert syndrome (JS) is an autosomal recessive ciliopathy characterized by hypotonia, ataxia, abnormal eye movements, and intellectual disability. The brain is malformed, with severe vermian hypoplasia, fourth ventriculomegaly, and “molar tooth” appearance of the cerebral and superior cerebellar peduncles visible as consistent features on neuroimaging. Neuropathological studies, though few, suggest that several other brain and spinal cord structures, such as the dorsal cervicomedullary junction, may also be affected in at least some patients. Genetically, JS is heterogeneous, with mutations in 13 genes accounting for approximately 50% of patients. Here, we compare neuropathologic findings in five subjects with JS, including four with defined mutations in OFD1 (2 siblings), RPGRIP1L, or TCTN2. Characteristic findings in all JS genotypes included vermian hypoplasia, fragmented dentate and spinal trigeminal nuclei, hypoplastic pontine and inferior olivary nuclei, and nondecussation of corticospinal tracts. Other common findings, seen in multiple genotypes but not all subjects, were dorsal cervicomedullary heterotopia, nondecussation of superior cerebellar peduncles, enlarged arcuate nuclei, hypoplastic reticular formation, hypoplastic medial lemnisci, and dorsal spinal cord disorganization. Thus, while JS exhibits significant neuropathologic as well as genetic heterogeneity, no genotype–phenotype correlations are apparent as yet. Our findings suggest that primary cilia are important for neural patterning, progenitor proliferation, cell migration, and axon guidance in the developing human brain and spinal cord.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR (2010) A method and server for predicting damaging missense mutations. Nat Methods 7:248–249

    Article  PubMed  CAS  Google Scholar 

  2. Altman NR, Naidich TP, Braffman BH (1992) Posterior fossa malformations. AJNR Am J Neuroradiol 13:691–724

    PubMed  CAS  Google Scholar 

  3. Baala L, Romano S, Khaddour R, Saunier S, Smith UM, Audollent S, Ozilou C, Faivre L, Laurent N, Foliguet B, Munnich A, Lyonnet S, Salomon R, Encha-Razavi F, Gubler MC, Boddaert N, de Lonlay P, Johnson CA, Vekemans M, Antignac C, Attie-Bitach T (2007) The Meckel–Gruber syndrome gene, MKS3, is mutated in Joubert syndrome. Am J Hum Genet 80:186–194

    Article  PubMed  CAS  Google Scholar 

  4. Boltshauser E, Isler W (1977) Joubert syndrome: episodic hyperpnea, abnormal eye movements, retardation and ataxia, associated with dysplasia of the cerebellar vermis. Neuropadiatrie 8:57–66

    Article  PubMed  CAS  Google Scholar 

  5. Brancati F, Dallapiccola B, Valente EM (2010) Joubert syndrome and related disorders. Orphanet J Rare Dis 5:20

    Article  PubMed  Google Scholar 

  6. Budny B, Chen W, Omran H et al (2006) A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral-facial-digital type I syndrome. Hum Genet 120:171–178

    Article  PubMed  CAS  Google Scholar 

  7. Calogero JA (1977) Vermian agenesis and unsegmented midbrain tectum. Case report. J Neurosurg 47:605–608

    Article  PubMed  CAS  Google Scholar 

  8. Campbell S, Tsannatos C, Pearce JM (1984) The prenatal diagnosis of Joubert’s syndrome of familial agenesis of the cerebellar vermis. Prenat Diagn 4:391–395

    Article  PubMed  CAS  Google Scholar 

  9. Caspary T, Larkins CE, Anderson KV (2007) The graded response to sonic hedgehog depends on cilia architecture. Develop Cell 12:767–778

    Article  CAS  Google Scholar 

  10. Chizhikov VV, Davenport J, Zhang Q et al (2007) Cilia proteins control cerebellar morphogenesis by promoting expansion of the granule progenitor pool. J Neurosci 27:9780–9789

    Article  PubMed  CAS  Google Scholar 

  11. Coene KL, Roepman R, Doherty D, Afroze B, Kroes HY, Letteboer SJ, Ngu LH, Budny B, van Wijk E, Gorden NT, Azhimi M, Thauvin-Robinet C, Veltman JA, Boink M, Kleefstra T, Cremers FP, van Bokhoven H, de Brouwer AP (2009) OFD1 is mutated in X-linked Joubert syndrome and interacts with LCA5-encoded lebercilin. Am J Hum Genet 85:465–481

    Article  PubMed  CAS  Google Scholar 

  12. Dafinger C, Liebau MC, Elsayed SM, Hellenbroich Y, Boltshauser E, Korenke GC, Fabretti F, Janecke AR, Ebermann I, Nürnberg G, Nürnberg P, Zentgraf H, Koerber F, Addicks K, Elsobky E, Benzing T, Schermer B, Bolz HJ (2011) Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog signaling and microtubule dynamics. J Clin Invest 121:2662–2667

    Article  PubMed  CAS  Google Scholar 

  13. Dahmane N, Sanchez P, Gitton Y, Palma V, Sun T, Beyna M, Weiner H, Ruiz i Altaba A (2001) The Sonic Hedgehog-Gli pathway regulates dorsal brain growth and tumorigenesis. Development 128:5201–5212

    PubMed  CAS  Google Scholar 

  14. Delous M, Baala L, Salomon R, Laclef C, Vierkotten J, Tory K, Golzio C, Lacoste T, Besse L, Ozilou C, Moutkine I, Hellman NE, Anselme I, Silbermann F, Vesque C, Gerhardt C, Rattenberry E, Wolf MT, Gubler MC, Martinovic J, Encha-Razavi F, Boddaert N, Gonzales M, Macher MA, Nivet H, Champion G, Bertheleme JP, Niaudet P, McDonald F, Hildebrandt F, Johnson CA, Vekemans M, Antignac C, Ruther U, Schneider-Maunoury S, Attie-Bitach T, Saunier S (2007) The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome. Nat Genet 39:875–881

    Article  PubMed  CAS  Google Scholar 

  15. Dixon-Salazar T, Silhavy JL, Marsh SE et al (2004) Mutations in the AHI1 gene, encoding Jouberin, cause Joubert syndrome with cortical polymicrogyria. Am J Hum Genet 75:979–987

    Article  PubMed  CAS  Google Scholar 

  16. Doherty D (2009) Joubert syndrome: insights into brain development, cilium biology, and complex disease. Semin Pediatr Neurol 16:143–154

    Article  PubMed  Google Scholar 

  17. Doherty D, Glass IA, Siebert JR, Strouse PJ, Parisi MA, Shaw DW, Chance PF, Barr M Jr, Nyberg D (2005) Prenatal diagnosis in pregnancies at risk for Joubert syndrome by ultrasound and MRI. Prenat Diagn 25:442–447

    Article  PubMed  Google Scholar 

  18. Doherty D, Parisi MA, Finn LS, Gunay-Aygun M, Al-Mateen M, Bates D, Clericuzio C, Demir H, Dorschner M, van Essen AJ, Gahl WA, Gentile M, Gorden NT, Hikida A, Knutzen D, Ozyurek H, Phelps I, Rosenthal P, Verloes A, Weigand H, Chance PF, Dobyns WB, Glass IA (2010) Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis). J Med Genet 47:8–21

    Article  PubMed  CAS  Google Scholar 

  19. Eggenschwiler JT, Anderson KV (2007) Cilia and developmental signaling. Annu Rev Cell Dev Biol 23:345–373

    Article  PubMed  CAS  Google Scholar 

  20. Exome Variant Server (2011) NHLBI Exome Sequencing Project (ESP), Seattle, WA. URL: http://snp.gs.washington.edu/EVS/. Accessed Sept. 2011

  21. Ferrante MI, Zullo A, Barra A, Bimonte S, Messaddeq N, Studer M, Dolle P, Franco B (2006) Oral-facial-digital type I protein is required for primary cilia formation and left–right axis specification. Nat Genet 38:112–117

    Article  PubMed  CAS  Google Scholar 

  22. Fluss J, Blaser S, Chitayat D, Akoury H, Glanc P, Skidmore M, Raybaud C (2006) Molar tooth sign in fetal brain magnetic resonance imaging leading to the prenatal diagnosis of Joubert syndrome and related disorders. J Child Neurol 21:320–324

    Article  PubMed  Google Scholar 

  23. Friede RL, Boltshauser E (1978) Uncommon syndromes of cerebellar vermis aplasia. I: Joubert syndrome. Dev Med Child Neurol 20:758–763

    Article  PubMed  CAS  Google Scholar 

  24. Garcia-Gonzalo FR, Corbit KC, Sirerol-Piquer MS, Ramaswami G, Otto EA, Noriega TR, Seol AD, Robinson JF, Bennett CL, Josifova DJ, García-Verdugo JM, Katsanis N, Hildebrandt F, Reiter JF (2011) A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition. Nat Genet 43:776–784

    Article  PubMed  CAS  Google Scholar 

  25. Giordano L, Vignoli A, Pinelli L, Brancati F, Accorsi P, Faravelli F, Gasparotti R, Granata T, Giaccone G, Inverardi F, Frassoni C, Dallapiccola B, Valente EM, Spreafico R (2009) Joubert syndrome with bilateral polymicrogyria: clinical and neuropathological findings in two brothers. Am J Med Genet A 149A:1511–1515

    Article  PubMed  CAS  Google Scholar 

  26. Gorden NT, Arts HH, Parisi MA, Coene KL, Letteboer SJ, van Beersum SE, Mans DA, Hikida A, Eckert M, Knutzen D, Alswaid AF, Ozyurek H, Dibooglu S, Otto EA, Liu Y, Davis EE, Hutter CM, Bammler TK, Farin FM, Dorschner M, Topcu M, Zackai EH, Rosenthal P, Owens KN, Katsanis N, Vincent JB, Hildebrandt F, Rubel EW, Raible DW, Knoers NV, Chance PF, Roepman R, Moens CB, Glass IA, Doherty D (2008) CC2D2A is mutated in Joubert syndrome and interacts with the ciliopathy-associated basal body protein CEP290. Am J Hum Genet 83:559–571

    Article  PubMed  CAS  Google Scholar 

  27. Goodship J, Platt J, Smith R et al (1991) A male with type I orofaciodigital syndrome. J Med Genet 28:691–694

    Article  PubMed  CAS  Google Scholar 

  28. Harting I, Kotzaeridou U, Poretti A, Seitz A, Pietz J, Bendszus M, Boltshauser E (2011) Interpeduncular heterotopia in Joubert syndrome: a previously undescribed MR finding. AJNR Am J Neuroradiol 32:1286–1289

    Article  PubMed  CAS  Google Scholar 

  29. Han YG, Spassky N, Romaguera-Ros M et al (2008) Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells. Nat Neurosci 11:277–284

    Article  PubMed  CAS  Google Scholar 

  30. Heninger E, Otto E, Imm A, Caridi G, Hildebrandt F (2001) Improved strategy for molecular genetic diagnostics in juvenile nephronophthisis. Am J Kidney Dis 37:1131–1139

    Article  PubMed  CAS  Google Scholar 

  31. Ishikawa T, Zhu BL, Li DR, Zhao D, Michiue T, Maeda H (2008) An autopsy case of an infant with Joubert syndrome who died unexpectedly and a review of the literature. Forensic Sci Int 179:e67–e73

    Article  PubMed  Google Scholar 

  32. Ivarsson SA, Bjerre I, Brun A, Ljungberg O, Maly E, Taylor I (1993) Joubert syndrome associated with Leber amaurosis and multicystic kidneys. Am J Med Genet 45:542–547

    Article  PubMed  CAS  Google Scholar 

  33. Joubert M, Eisenring JJ, Robb JP, Andermann F (1969) Familial agenesis of the cerebellar vermis. A syndrome of episodic hyperpnea, abnormal eye movements, ataxia, and retardation. Neurology 19:813–825

    PubMed  CAS  Google Scholar 

  34. Koirala S, Jin Z, Piao X, Corfas G (2009) GPR56-regulated granule cell adhesion is essential for rostral cerebellar development. J Neurosci 29:7439–7449

    Article  PubMed  CAS  Google Scholar 

  35. Kumandas S, Akcakus M, Coskun A, Gumus H (2004) Joubert syndrome: review and report of seven new cases. Eur J Neurol 11:505–510

    Article  PubMed  CAS  Google Scholar 

  36. Lancaster MA, Gopal DJ, Kim J, Saleem SN, Silhavy JL, Louie CM, Thacker BE, Williams Y, Zaki MS, Gleeson JG (2011) Defective Wnt-dependent cerebellar midline fusion in a mouse model of Joubert syndrome. Nat Med 17:726–731

    Article  PubMed  CAS  Google Scholar 

  37. Liu JS (2011) Molecular genetics of neuronal migration disorders. Curr Neurol Neurosci Rep 11(2):171–178

    Article  PubMed  CAS  Google Scholar 

  38. Lopes CA, Prosser SL, Romio L, Hirst RA, O’Callaghan C, Woolf AS, Fry AM (2011) Centriolar satellites are assembly points for proteins implicated in human ciliopathies, including oral-facial-digital syndrome 1. J Cell Sci 124:600–612

    Article  PubMed  CAS  Google Scholar 

  39. Maria BL, Quisling RG, Rosainz LC, Yachnis AT, Gitten J, Dede D, Fennell E (1999) Molar tooth sign in Joubert syndrome: clinical, radiologic, and pathologic significance. J Child Neurol 14:368–376

    Article  PubMed  CAS  Google Scholar 

  40. McGraw P (2003) The molar tooth sign. Radiology 229:671–672

    Article  PubMed  Google Scholar 

  41. Millen KJ, Gleeson JG (2008) Cerebellar development and disease. Curr Opin Neurobiol 18:12–19

    Article  PubMed  CAS  Google Scholar 

  42. Ocbina PJR, Anderson KV (2008) Intraflagellar transport, cilia and mammalian Hedgehog signaling: analysis in mouse embryonic fibroblasts. Dev Dyn 237:2030–2038

    Article  PubMed  Google Scholar 

  43. Padgett KR, Maria BL, Yachnis AT, Blackband SJ (2002) Ex vivo high-resolution magnetic resonance imaging of the brain in Joubert’s syndrome. J Child Neurol 17:911–913

    Article  PubMed  Google Scholar 

  44. Parisi MA, Dobyns WB (2003) Human malformations of the midbrain and hindbrain: review and proposed classification scheme. Mol Genet Metab 80:36–53

    Article  PubMed  CAS  Google Scholar 

  45. Parisi MA, Doherty D, Chance PF, Glass IA (2007) Joubert syndrome (and related disorders) (OMIM 213300). Eur J Hum Genet 15:511–521

    Article  PubMed  CAS  Google Scholar 

  46. Poretti A, Brehmer U, Scheer I et al (2008) Prenatal and neonatal MR imaging findings in oral-facial-digital syndrome type VI. AJNR 29:1090–1091

    Article  PubMed  CAS  Google Scholar 

  47. Poretti A, Huisman TA, Scheer I, Boltshauser E (2011) Joubert syndrome and related disorders: spectrum of neuroimaging findings in 75 patients. AJNR Am J Neuroradiol 32:1459–1463

    Article  PubMed  CAS  Google Scholar 

  48. Prattichizzo C, Macca M, Novelli V, Giorgio G, Barra A, Franco B, Oral-Facial-Digital Type ICG (2008) Mutational spectrum of the oral-facial-digital type I syndrome: a study on a large collection of patients. Hum Mutat 29:1237–1246

    Article  PubMed  CAS  Google Scholar 

  49. Putoux A, Thomas S, Coene KL, Davis EE, Alanay Y, Ogur G, Uz E, Buzas D, Gomes C, Patrier S, Bennett CL, Elkhartoufi N, Frison MH, Rigonnot L, Joyé N, Pruvost S, Utine GE, Boduroglu K, Nitschke P, Fertitta L, Thauvin-Robinet C, Munnich A, Cormier-Daire V, Hennekam R, Colin E, Akarsu NA, Bole-Feysot C, Cagnard N, Schmitt A, Goudin N, Lyonnet S, Encha-Razavi F, Siffroi JP, Winey M, Katsanis N, Gonzales M, Vekemans M, Beales PL, Attié-Bitach T (2011) KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes. Nat Genet 43:601–606

    Article  PubMed  CAS  Google Scholar 

  50. Quisling RG, Barkovich AJ, Maria BL (1999) Magnetic resonance imaging features and classification of central nervous system malformations in Joubert syndrome. J Child Neurol 14:628–635 (discussion 669–672)

    Article  PubMed  CAS  Google Scholar 

  51. Ribes V, Stutzmann F, Bianchetti L, Guillemot F, Dolle P, Le Roux I (2008) Combinatorial signaling controls Neurogenin2 expression at the onset of spinal neurogenesis. Dev Biol 321:470–481

    Article  PubMed  CAS  Google Scholar 

  52. Romano S, Boddaert N, Desguerre I, Hubert L, Salomon R, Seidenwurm D, Bahi-Buisson N, Nabbout R, Sonigo P, Lyonnet S, Brunelle F, Munnich A, de Lonlay P (2006) Molar tooth sign and superior vermian dysplasia: a radiological, clinical, and genetic study. Neuropediatrics 37:42–45

    Article  PubMed  CAS  Google Scholar 

  53. Saleem SN, Zaki MS (2010) Role of MR imaging in prenatal diagnosis of pregnancies at risk for Joubert syndrome and related cerebellar disorders. AJNR Am J Neuroradiol 31:424–429

    Article  PubMed  CAS  Google Scholar 

  54. Saleem SN, Zaki MS, Soliman NA, Momtaz M (2011) Prenatal magnetic resonance imaging diagnosis of molar tooth sign at 17 to 18 weeks of gestation in two fetuses at risk for Joubert syndrome and related cerebellar disorders. Neuropediatrics 42:35–38

    Article  PubMed  CAS  Google Scholar 

  55. Sang L, Miller JJ, Corbit KC, Giles RH, Brauer MJ, Otto EA, Baye LM, Wen X, Scales SJ, Kwong M, Huntzicker EG, Sfakianos MK, Sandoval W, Bazan JF, Kulkarni P, Garcia-Gonzalo FR, Seol AD, O’Toole JF, Held S, Reutter HM, Lane WS, Rafiq MA, Noor A, Ansar M, Devi AR, Sheffield VC, Slusarski DC, Vincent JB, Doherty DA, Hildebrandt F, Reiter JF, Jackson PK (2011) Mapping the NPHP–JBTS–MKS protein network reveals ciliopathy disease genes and pathways. Cell 145:513–528

    Article  PubMed  CAS  Google Scholar 

  56. Saraiva JM, Baraitser M (1992) Joubert syndrome: a review. Am J Med Genet 43:726–731

    Article  PubMed  CAS  Google Scholar 

  57. Sattar S, Gleeson JG (2011) The ciliopathies in neuronal development: a clinical approach to investigation of Joubert syndrome and Joubert syndrome-related disorders. Dev Med Child Neurol 53:793–798

    Article  PubMed  Google Scholar 

  58. Sawamoto K, Wichterie H, Gonzalez-Perez O et al (2006) New neurons follow the flow of cerebrospinal fluid in the adult brain. Science 311:629–632

    Article  PubMed  CAS  Google Scholar 

  59. Schneider L, Cammer M, Lehman J et al (2010) Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts. Cell Physiol Biochem 25:279–292

    Article  PubMed  CAS  Google Scholar 

  60. Senocak EU, Oguz KK, Haliloglu G, Topcu M, Cila A (2010) Structural abnormalities of the brain other than molar tooth sign in Joubert syndrome-related disorders. Diagn Interv Radiol 16:3–6

    PubMed  Google Scholar 

  61. Singla V, Romaguera-Ros M, Garcia-Verdugo JM, Reiter JF (2010) Ofd1, a human disease gene, regulates the length and distal structure of centrioles. Dev Cell 18:410–424

    Article  PubMed  CAS  Google Scholar 

  62. Spassky N, Han YG, Aguilar A, Strehl L, Besse L, Laclef C, Ros MR, Garcia-Verdugo JM, Alvarez-Buylla A (2008) Primary cilia are required for cerebellar development and Shh-dependent expansion of progenitor pool. Dev Biol 317:246–259

    Article  PubMed  CAS  Google Scholar 

  63. Sztriha L, Al-Gazali LI, Aithala GR, Nork M (1999) Joubert’s syndrome: new cases and review of clinicopathologic correlation. Pediatr Neurol 20:274–281

    Article  PubMed  CAS  Google Scholar 

  64. ten Donkelaar HJ, Hoevenaars F, Wesseling P (2000) A case of Joubert’s syndrome with extensive cerebral malformations. Clin Neuropathol 19:85–93

    PubMed  Google Scholar 

  65. ten Donkelaar HJ, Lammens M (2009) Development of the human cerebellum and its disorders. Clin Perinatol 36:513–530

    Article  PubMed  Google Scholar 

  66. Valente EM, Logan CV, Mougou-Zerelli S, Lee JH, Silhavy JL, Brancati F, Iannicelli M, Travaglini L, Romani S, Illi B, Adams M, Szymanska K, Mazzotta A, Lee JE, Tolentino JC, Swistun D, Salpietro CD, Fede C, Gabriel S, Russ C, Cibulskis K, Sougnez C, Hildebrandt F, Otto EA, Held S, Diplas BH, Davis EE, Mikula M, Strom CM, Ben-Zeev B, Lev D, Sagie TL, Michelson M, Yaron Y, Krause A, Boltshauser E, Elkhartoufi N, Roume J, Shalev S, Munnich A, Saunier S, Inglehearn C, Saad A, Alkindy A, Thomas S, Vekemans M, Dallapiccola B, Katsanis N, Johnson CA, Attie-Bitach T, Gleeson JG (2010) Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes. Nat Genet 42:619–625

    Article  PubMed  CAS  Google Scholar 

  67. van Dorp DB, Palan A, Kwee ML, Barth PG, van der Harten JJ (1991) Joubert syndrome: a clinical and pathological description of an affected male and a female fetus from the same sibship. Am J Med Genet 40:100–104

    Article  PubMed  Google Scholar 

  68. Watanabe H, Murakami F (2009) Real time analysis of pontine neurons during initial stages of nucleogenesis. Neurosci Res 64:20–29

    Article  PubMed  Google Scholar 

  69. Yachnis AT, Rorke LB (1999) Neuropathology of Joubert syndrome. J Child Neurol 14:655–659 (discussion 669–672)

    Article  PubMed  CAS  Google Scholar 

  70. Yu W, McDonnell K, Taketo MM, Bai CB (2008) Wnt signaling determines ventral spinal cord cell fates in a time-dependent manner. Development 135:3687–3696

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank the families of described subjects for giving us permission to study their children. We also thank Drs. Joseph R. Siebert, Raj P. Kapur (Seattle Children’s Hospital and University of Washington, Seattle, WA), Robert E. Ruiz (The University of Michigan Hospitals, Ann Arbor, MI), Carol Petito (University of Miami, Miami, Fl), Mason Barr (University of Michigan) and colleagues from the Wayne County Medical Examiner’s Office (Romulus, MI) for important assistance to our research. Human tissue was obtained from the NICHD Brain and Tissue bank for Developmental Disorders at the University of Maryland, Baltimore, MD. D.D. was supported by KL2RR025015.

Author information

Authors and Affiliations

  1. Department of Neurological Surgery, Seattle Children’s Research Institute, University of Washington, Box C9S-10, 1900 Ninth Ave, Seattle, WA, 98101, USA

    Gordana Juric-Sekhar & Robert F. Hevner

  2. Department of Pediatrics, Seattle Children’s Research Institute, University of Washington, Seattle, WA, USA

    Jonathan Adkins & Dan Doherty

Authors
  1. Gordana Juric-Sekhar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jonathan Adkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dan Doherty
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert F. Hevner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Dan Doherty or Robert F. Hevner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Juric-Sekhar, G., Adkins, J., Doherty, D. et al. Joubert syndrome: brain and spinal cord malformations in genotyped cases and implications for neurodevelopmental functions of primary cilia. Acta Neuropathol 123, 695–709 (2012). https://doi.org/10.1007/s00401-012-0951-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-012-0951-2

Keywords

Search

Navigation