Joubert syndrome-derived induced pluripotent stem cells show altered neuronal differentiation in vitro
Cell Tissue Res. 2024 Mar 19. doi: 10.1007/s00441-024-03876-9. Online ahead of print.ABSTRACTJoubert syndrome (JS) is a recessively inherited congenital ataxia characterized by hypotonia, psychomotor delay, abnormal ocular movements, intellectual disability, and a peculiar cerebellar and brainstem malformation, the "molar tooth sign." Over 40 causative genes have been reported, all encoding for proteins implicated in the structure or functioning of the primary cilium, a subcellular organelle widely present in embryonic and adult tissues. In this paper, we developed an in vitro neuronal differentiation model using patient-d...
Source: Cell Research - March 19, 2024 Category: Cytology Authors: Roberta De Mori Silvia Tardivo Lidia Pollara Silvia Clara Giliani Eltahir Ali Lucio Giordano Vincenzo Leuzzi Rita Fischetto Blanca Gener Santo Diprima Marco J Morelli Maria Cristina Monti Virginie Sottile Enza Maria Valente Source Type: research
Joubert syndrome-derived induced pluripotent stem cells show altered neuronal differentiation in vitro
AbstractJoubert syndrome (JS) is a recessively inherited congenital ataxia characterized by hypotonia, psychomotor delay, abnormal ocular movements, intellectual disability, and a peculiar cerebellar and brainstem malformation, the “molar tooth sign.” Over 40 causative genes have been reported, all encoding for proteins implicated in the structure or functioning of the primary cilium, a subcellular organelle widely present in embryonic and adult tissues. In this paper, we developed anin vitro neuronal differentiation model using patient-derived induced pluripotent stem cells (iPSCs), to evaluate possible neurodevelopme...
Source: Cell and Tissue Research - March 19, 2024 Category: Cytology Source Type: research
Joubert syndrome causing mutation in C2 domain of CC2D2A affects structural integrity of cilia and cellular signaling molecules
Exp Brain Res. 2024 Jan 17. doi: 10.1007/s00221-023-06762-y. Online ahead of print.ABSTRACTCilia are organelles extend from cells to sense external signals for tuning intracellular signaling for optimal cellular functioning. They have evolved sensory and motor roles in various cells for tissue organization and homeostasis in development and post-development. More than a thousand genes are required for cilia function. Mutations in them cause multisystem disorders termed ciliopathies. The null mutations in CC2D2A result in Meckel syndrome (MKS), which is embryonic lethal, whereas patients who have missense mutations in the C...
Source: Experimental Brain Research - January 17, 2024 Category: Neuroscience Authors: Roopasree O Jayarajan Soura Chakraborty Kozhiparambil Gopalan Raghu Jayamurthy Purushothaman Shobi Veleri Source Type: research
A case with Joubert syndrome diagnosed at an advanced age
Med Clin (Barc). 2023 Dec 19:S0025-7753(23)00672-3. doi: 10.1016/j.medcli.2023.11.001. Online ahead of print.NO ABSTRACTPMID:38123406 | DOI:10.1016/j.medcli.2023.11.001 (Source: Medicina Clinica)
Source: Medicina Clinica - December 20, 2023 Category: General Medicine Authors: Kadir Intas Gulay Ulusal Okyay Mehmet Deniz Ayli Source Type: research
Generation of iPSC line from a Joubert syndrome patient with compound heterozygous mutations in CPLANE1 gene
Stem Cell Res. 2023 Dec 2;74:103267. doi: 10.1016/j.scr.2023.103267. Online ahead of print.ABSTRACTWe generated iPSC line using skin fibroblasts obtained from a female patient affected by Joubert syndrome, caused by two compound heterozygous variants (c.143G > A; p.Gly48Glu and c.1784 T > G; p.Leu595Ter) in CPLANE1. We used Sendai-virus-based technique for reprogramming and then we applied karyotype analysis, to exclude possible acquired big rearrangements. We verified the presence of the same STR profile as fibroblasts, the stem cell state (by immunofluorescence and qPCR) and, finally, the pluripotency state (by in ...
Source: Cell Research - December 15, 2023 Category: Cytology Authors: Mazzotta C Serpieri V Orsi A Cavan S Rossi E Stanzial F Valente E M Source Type: research
Macrocephaly? Don ’t forget SUFU
Pathogenic variants in SUFU (suppressor of fused homolog) are regularly identified in tumour samples and are linked with malignancy by disinhibition of the Sonic Hedgehog (SHH) signalling pathway.(1) In rare cases heterozygous germline variants in SUFU are identified. This heterozygous state is associated with predisposition for various malignancies. The overall risk for tumour development (of any type) in heterozygous individuals is around 68%.(2) Early onset medulloblastoma is the most common tumour type found in 50% of the patients with a median age of 18 months at diagnosis.(2) In addition to predisposition to malignan...
Source: Pediatric Neurology - November 24, 2023 Category: Neurology Authors: Ellen Rijckmans, Victoria Bordon, Thomy de Ravel, Elien Baert, Anna C. Jansen, Katrien Stouffs Tags: Correspondence Source Type: research
A novel mutation of the RPGRIP1L gene in a Chinese boy with Joubert syndrome with oculorenal involvement
Joubert syndrome (JS) is a rare genetically heterogeneous primary ciliopathy characterized by a pathognomonic cerebellar and brainstem malformation, the “molar tooth sign”, and variable organ involvement (such... (Source: BMC Pediatrics)
Source: BMC Pediatrics - November 23, 2023 Category: Pediatrics Authors: Qian Li, Qianying Liu, Suwen Liu, Lichun Yu, Zhenle Yang, Cong Wang, Jing Wang and Shuzhen Sun Tags: Case Report Source Type: research
Novel variants identified in five Chinese families with Joubert Syndrome: a case report
Joubert syndrome (JS) is a group of rare ciliopathies, mainly characterized by cerebellar dysplasia representing the “molar tooth sign (MTS)” on neuroimaging, hypotonia, and developmental delay. Having a compl... (Source: BMC Medical Genomics)
Source: BMC Medical Genomics - September 21, 2023 Category: Genetics & Stem Cells Authors: Liwei Fang, Lulu Wang, Li Yang, Xiaoyan Xu, Shanai Pei and De Wu Tags: Case Report Source Type: research
Identification of novel TMEM231 gene splice variants and pathological findings in a fetus with Meckel Syndrome
Conclusion: We reported the clinical, genetic, molecular and histochemical characterisation of a family affected by MKS. Our findings not only extended the mutation spectrum of the TMEM231 gene, but also revealed for the first time the pathological aetiology of primary cilia in humans and provide a basis for genetic counselling of the parents to their offspring. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - September 6, 2023 Category: Genetics & Stem Cells Source Type: research
An early onset cone dystrophy due to CEP290 mutation: a case report
ConclusionsCEP290 mutation causes a wide variety of clinical phenotypes. The presented case shows a phenotype resembling achromatopsia or early onset slowly progressing cone dystrophy. (Source: Documenta Ophthalmologica)
Source: Documenta Ophthalmologica - August 29, 2023 Category: Opthalmology Source Type: research
Recurrent, founder and hypomorphic variants contribute to the genetic landscape of Joubert syndrome
Conclusion
This study contributes to understand the complex genetic landscape of JS, explain its variable prevalence in distinct geographical areas and characterise two recurrent hypomorphic variants. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - August 21, 2023 Category: Genetics & Stem Cells Authors: Serpieri, V., Mortarini, G., Loucks, H., Biagini, T., Micalizzi, A., Palmieri, I., Dempsey, J. C., DAbrusco, F., Mazzotta, C., Battini, R., Bertini, E. S., Boltshauser, E., Borgatti, R., Brockmann, K., D'Arrigo, S., Nardocci, N., Fischetto, R., Agolini, E Tags: Open access Neurogenetics Source Type: research
Human Mutations in Arl3, a Small GTPase Involved in Lipidated Cargo Delivery to the Cilia, Cause Retinal Dystrophy
Adv Exp Med Biol. 2023;1415:283-288. doi: 10.1007/978-3-031-27681-1_41.ABSTRACTPhotoreceptors are highly polarized sensory neurons. Precise localization of signaling molecules within the ciliary outer segment is critical for photoreceptor function and viability. The small GTPase Arl3 plays a particularly important role in photoreceptors as it regulates outer segment enrichment of lipidated proteins essential for the visual response: transducin-α, transducin-γ, PDEα, PDE β, and Grk1. Recently, mutations in Arl3 have been identified in human patients with nonsyndromic autosomal recessive and dominant inherited retinal de...
Source: Advances in Experimental Medicine and Biology - July 13, 2023 Category: Research Authors: Amanda M Travis Jillian N Pearring Source Type: research
New Insights into the Neuropsychological Profile and Intellectual Quotient Variability in Joubert Syndrome Compared to Other Congenital Cerebellar Malformations
Cerebellum. 2023 Jun 23. doi: 10.1007/s12311-023-01580-y. Online ahead of print.ABSTRACTThe neuropsychological characteristics of the cerebellar cognitive affective syndrome (CCAS) in congenital, non-progressive malformations of the cerebellum have been scarcely investigated, and even less is known for Joubert syndrome (JS), an inherited, non-progressive cerebellar ataxia characterized by the so-called molar tooth sign. The few studies on this topic reported inconsistent results about intellectual functioning and specific neuropsychological impairments. The aim of this research is to examine the neuropsychological profile ...
Source: Cerebellum - June 23, 2023 Category: Neuroscience Authors: Niccol ò Butti Viola Oldrati Elisabetta Ferrari Romina Romaniello Chiara Gagliardi Renato Borgatti Cosimo Urgesi Source Type: research
