The ciliopathies in neuronal development: a clinical approach to investigation of Joubert syndrome and Joubert syndrome‐related disorders

SATTAR, SHIFTEH; GLEESON, JOSEPH G

doi:10.1111/j.1469-8749.2011.04021.x

Cited by 155Genetic and Kidney Cyst DiseasesCystic Fibrosis Research AdvancesHereditary Neurological Disorders

The ciliopathies in neuronal development: a clinical approach to investigation of Joubert syndrome and Joubert syndrome‐related disorders

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SATTAR, SHIFTEH, GLEESON, JOSEPH G·2011·Developmental Medicine & Child Neurology

DOI 10.1111/j.1469-8749.2011.04021.xPMC PMC3984879

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Abstract

A group of disorders with disparate symptomatology, including congenital cerebellar ataxia, retinal blindness, liver fibrosis, polycystic kidney disease, and polydactyly, have recently been united under a single disease mechanism called ‘ciliopathies’. The ciliopathies are due to defects of the cellular antenna known as the primary cilium, a microtubule‐based extension of cellular membranes found in nearly all cell types. Key among these ciliopathies is Joubert syndrome, displaying ataxia, oculomotor apraxia, and mental retardation* with a pathognomonic ‘molar tooth sign’ on brain magnetic resonance imaging. The importance of ciliary function in neuronal development has been appreciated only in the last decade with the classification of Joubert syndrome as a ciliopathy. This, together with the identification of many of the clinical features of ciliopathies in individuals with Joubert syndrome and the localization of Joubert syndrome’s causative gene products at or near the primary cilium, have defined a new class of neurological disease. Cilia are involved in diverse cellular processes including protein trafficking, photoreception, embryonic axis patterning, and cell cycle regulation. Ciliary dysfunction can affect a single tissue or manifest as multi‐organ involvement. Ciliary defects have been described in retinopathies such as retinitis pigmentosa and Leber congenital amaurosis (defects in photoreceptor ciliary protein complexes), renal syndromes with nephronophthisis and cystic dysplastic kidneys, and liver conditions such as fibrosis and biliary cirrhosis. Recognizing the diverse presentations of the ciliopathies and screening strategies following diagnosis is an important part of the treatment plan of children with cilia‐related disorders.

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All ciliopathies share one phenotype, cognitive impairment.
“All ciliopathies share one phenotype, cognitive impairment [37–42].”
From Amyloid-β interrupts canonical Sonic hedgehog signaling by distorting primary cilia structure (2018) · cites this paper as [38]
The Abstract describes ciliopathies as having disparate symptoms and says ciliary dysfunction can affect a single tissue, including in retinal disorders. It identifies cognitive impairment in particular ciliopathies, such as Joubert syndrome, but does not present it as a phenotype shared by all ciliopathies. (LLM, conf=0.86)
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Impaired Shh signaling results in similar phenotypes as those observed in patients with disrupted cilia structure or function.
“Impaired Shh signaling results in similar phenotypes as those observed in patients with disrupted cilia structure or function [37–42].”
From Amyloid-β interrupts canonical Sonic hedgehog signaling by distorting primary cilia structure (2018) · cites this paper as [38]
The Abstract says defects in ciliary proteins adversely affect Sonic hedgehog signalling and describes phenotypes associated with ciliary defects. It does not establish that impaired Sonic hedgehog signalling produces similar phenotypes; it explicitly says the extent to which altered signalling leads to clinical presentation is unknown. No page number is available in our copy. (LLM, conf=0.85)
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Research works printed but not linked: 1

[1]Joubert M Eisenring JJ Andermann F Familial dysgenesis of the vermis: a syndrome of hyperventilation, abnormal eye movements and retardation Neurology 1968 18 302 3 5690407

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Authors: SATTAR, S., & GLEESON, J. G.
Affiliations: University of California San Diego (US)
Corresponding author: GLEESON, JOSEPH G
ORCID: SATTAR, SHIFTEH
GLEESON, JOSEPH G
Venue: Developmental Medicine & Child Neurology
Publisher: Wiley
Published: 2011-06-17
Volume: 53
Issue: 9
Pages: 793-798
ISSN: 0012-1622 (ISSN-L)
1469-8749
DOI: 10.1111/j.1469-8749.2011.04021.x
PMC: PMC3984879
OpenAlex: W2004044775
Cited by: 155
References: 32
Citations by year: 2026: 1 · 2025: 11 · 2024: 10 · 2023: 13 · 2022: 9 · 2021: 6 · 2020: 9 · 2019: 8 · 2018: 5 · 2017: 13 · 2016: 10 · 2015: 7 · 2014: 14 · 2013: 14 · 2012: 24
FWCI: 1.80
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Developmental Medicine & Child Neurology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Howard Hughes Medical Institute
National Institute of Neurological Disorders and Stroke (R01NS048453, R01NS052455)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
Keywords: ciliopathies, Joubert syndrome, neuronal development, primary cilia, molar tooth sign, oculomotor apraxia, retinitis pigmentosa, Leber congenital amaurosis, nephronophthisis, polycystic kidney disease, liver fibrosis, biliary cirrhosis, ciliary dysfunction, screening, embryonic axis patterning
MeSH terms: Apraxias, Cerebellar Diseases, Cilia, Ciliary Motility Disorders, Eye Abnormalities, Humans, Magnetic Resonance Imaging, Orofaciodigital Syndromes, Bardet-Biedl Syndrome, Cogan Syndrome, Leber Congenital Amaurosis

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The ciliopathies in neuronal development: a clinical approach to investigation of Joubert syndrome and Joubert syndrome‐related disorders

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