Joubert syndrome: review and report of seven new cases

Kumandaş, Sefer; Akçakuş, Mustafa; Çoşkun, Abdulhakim; Gümüş, Haluk

doi:10.1111/j.1468-1331.2004.00819.x

Cited by 41 publications

(40 citation statements)

References 23 publications

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“…In the light green module, we also identified INPP5E, a gene involved in phosphatidylinositol signaling system and known to mobilize intracellular calcium. Mutation of this gene leads to Joubert syndrome, which is a rare monogenic condition with high penetrance for ASD [70][71][72][73]. In summary, both down-and upregulated modules in TS show changes parallel with those observed in postmortem brain of idiopathic ASD, consistent with the existence of convergent molecular pathways in multiple forms of ASD [74].…”

Section: Gene Co-expression Modules Dissect Pathways Related To Diffementioning

confidence: 72%

Alteration in basal and depolarization induced transcriptional network in iPSC derived neurons from Timothy syndrome

et al. 2014

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Background: Common genetic variation and rare mutations in genes encoding calcium channel subunits have pleiotropic effects on risk for multiple neuropsychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia. To gain further mechanistic insights by extending previous gene expression data, we constructed co-expression networks in Timothy syndrome (TS), a monogenic condition with high penetrance for ASD, caused by mutations in the L-type calcium channel, Ca v 1.2. Methods: To identify patient-specific alterations in transcriptome organization, we conducted a genome-wide weighted co-expression network analysis (WGCNA) on neural progenitors and neurons from multiple lines of induced pluripotent stem cells (iPSC) derived from normal and TS (G406R in CACNA1C) individuals. We employed transcription factor binding site enrichment analysis to assess whether TS associated co-expression changes reflect calcium-dependent co-regulation.

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Section: Gene Co-expression Modules Dissect Pathways Related To Diffementioning

confidence: 72%

Alteration in basal and depolarization induced transcriptional network in iPSC derived neurons from Timothy syndrome

et al. 2014

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“…A variety of other abnormalities has been described in children with JBTS, with different levels of severity, including a characteristic facial appearance, delayed language, hypersensitivity to noise, autism, ocular and oculomotor abnormalities, meningoencephaloceles, microcephaly, low-set ears, polydactyly, retinal dysplasia, kidney abnormalities (renal cysts), soft-tissue tumours of the tongue, liver disease (including fibrocystic changes) and duodenal atresia 38. Several of these features overlap with those described for MKS including, in particular, the classic MKS features of polydactyly, fibrocystic changes to the liver and encephalocele.…”

Section: A Phenotypic Spectrum Of Disease Severity: Joubert Syndrome mentioning

confidence: 99%

Recent advances in the molecular pathology, cell biology and genetics of ciliopathies

Adams

Smith

Logan

et al. 2008

Journal of Medical Genetics

133

101

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Primary cilia have a broad tissue distribution and are present on most cell types in the human body. Until recently, they were considered to be redundant organelles, but progress over the past 5 years has led to an understanding of their role in normal mammalian development. The class of inherited disorders that involve aberrant ciliary function are known as ciliopathies, and although their range of severity can vary, they share some common and unexpected clinical phenotypes. The aim of this review is to assess recent insights into the structure, function and formation of primary cilia, and relate this to the pathology, molecular genetics and cell biology of the ciliopathies.

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“…Affected patients manifest early hypotonia followed by ataxia, episodic apnea and/or hyperpnea, abnormal eye movements, developmental delay, and intellectual disability. In addition, retinal dystrophy, hepatic fibrosis, cystic kidneys, endocrine abnormalities, encephalocele and polydactyly are seen in some patients [5,8,16,32,33,35,45,63]. The ''molar tooth'' sign (MTS) on axial magnetic resonance imaging (MRI) is key to the diagnosis of JS [39,40,43,44,49,50,52,60].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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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.

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Joubert syndrome: review and report of seven new cases

Cited by 41 publications

References 23 publications

Alteration in basal and depolarization induced transcriptional network in iPSC derived neurons from Timothy syndrome

Alteration in basal and depolarization induced transcriptional network in iPSC derived neurons from Timothy syndrome

Recent advances in the molecular pathology, cell biology and genetics of ciliopathies

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

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