OFD Type I syndrome: lessons learned from a rare ciliopathy.
Abstract
The OFD1 gene was initially identified as the gene responsible for the X-linked dominant male lethal OFD type I syndrome, a developmental disorder ascribed to cilia disfunction. The transcript has been subsequently associated to four different X-linked recessive conditions, namely Joubert syndrome, retinitis pigmentosa, primary ciliary dyskinesia and Simpson-Golabi-Behmel type 2 syndrome. The centrosomal/basal body OFD1 protein has indeed been shown to be required for primary cilia formation and left-right asymmetry. The protein is also involved in other tasks, e.g. regulation of cellular protein ...
Source: Biochemical Society Transactions - September 7, 2020 Category: Biochemistry Authors: Morleo M, Franco B Tags: Biochem Soc Trans Source Type: research
The Joubert Syndrome Gene arl13b is Critical for Early Cerebellar Development in Zebrafish
AbstractJoubert syndrome is characterized by unique malformation of the cerebellar vermis. More than thirty Joubert syndrome genes have been identified, includingARL13B. However, its role in cerebellar development remains unexplored. We found that knockdown or knockout ofarl13b impaired balance and locomotion in zebrafish larvae. Granule cells were selectively reduced in the corpus cerebelli, a structure homologous to the mammalian vermis. Purkinje cell progenitors were also selectively disturbed dorsomedially. The expression ofatoh1 andptf1, proneural genes of granule and Purkinje cells, respectively, were selectively dow...
Source: Neuroscience Bulletin - August 17, 2020 Category: Neuroscience Source Type: research
RE: Clinical and Molecular Diagnosis of Joubert Syndrome and Related Disorders
Sir, (Source: Pediatric Neurology)
Source: Pediatric Neurology - July 22, 2020 Category: Neurology Authors: Miguel Barroso-Gil, Laura Powell, John A. Sayer Tags: Correspondence Source Type: research
Dysfunction of the ciliary ARMC9/TOGARAM1 protein module causes Joubert syndrome
Joubert syndrome (JBTS) is a recessive neurodevelopmental ciliopathy characterized by a pathognomonic hindbrain malformation. All known JBTS genes encode proteins involved in the structure or function of primary cilia, ubiquitous antenna-like organelles essential for cellular signal transduction. Here, we used the recently identified JBTS-associated protein armadillo repeat motif–containing 9 (ARMC9) in tandem-affinity purification and yeast 2-hybrid screens to identify a ciliary module whose dysfunction underlies JBTS. In addition to the known JBTS-associated proteins CEP104 and CSPP1, we identified coiled-coil domain c...
Source: Journal of Clinical Investigation - July 21, 2020 Category: Biomedical Science Authors: Brooke L. Latour, Julie C. Van De Weghe, Tamara D.S. Rusterholz, Stef J.F. Letteboer, Arianna Gomez, Ranad Shaheen, Matthias Gesemann, Arezou Karamzade, Mostafa Asadollahi, Miguel Barroso-Gil, Manali Chitre, Megan E. Grout, Jeroen van Reeuwijk, Sylvia E.C Source Type: research
Electroretinographic Assessment in Joubert Syndrome: A Suggested Objective Method to Evaluate the Effectiveness of Future Targeted Treatment
ConclusionsOur results suggest that a dysfunction of photoreceptors and bipolar cells occurs in patients with JS with or without retinal dystrophy. The retinal impairment can be detected by ERG recordings and this method should be proposed to evaluate the effectiveness of adequate treatment targeted to improve the retinal impairment in patients with JS. (Source: Advances in Therapy)
Source: Advances in Therapy - July 14, 2020 Category: Drugs & Pharmacology Source Type: research
Two novel B9D1 variants causing Joubert syndrome: Utility of mRNA and splicing studies.
This report outlines an interesting case of JS, in which two novel mutations in B9D1 were identified. This gene is not commonly associated with JS, and is often implicated in MKS. Functional mRNA study was helpful in delineating the pathogenic role of novel variants in this case.
PMID: 32622957 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - July 1, 2020 Category: Genetics & Stem Cells Authors: Katiyar D, Anderson N, Bournazos A, Cooper S, Goel H Tags: Eur J Med Genet Source Type: research
Clinical features and molecular genetics of autosomal recessive ataxia in the Turkish population
Conclusion: The prevalence of hereditary ataxia can vary among countries. The consanguineous marriage is an important finding in these diseases. These genetic tests will increase the number of ARCA patients diagnosed. (Source: Journal of Pediatric Neurosciences)
Source: Journal of Pediatric Neurosciences - June 29, 2020 Category: Neuroscience Authors: Faruk Incecik Ozlem M Herguner Neslihan O Mungan Source Type: research
Morpho-functional survey in children suspected of inherited retinal dystrophies via video recording, electrophysiology and genetic analysis
ConclusionFundus imaging associated with ERG may be significant in IRD diagnosis and visual impairment prognosis, alongside genetic analysis and therapy in selected cases. (Source: International Ophthalmology)
Source: International Ophthalmology - June 6, 2020 Category: Opthalmology Source Type: research
Sudden death in epilepsy and ectopic neurohypophysis in Joubert syndrome 23 diagnosed using SNVs/indels and structural variants pipelines on WGS data: a case report
Joubert syndrome (JBTS) is a genetically heterogeneous group of neurodevelopmental syndromes caused by primary cilia dysfunction. Usually the neurological presentation starts with abnormal neonatal breathing f... (Source: BMC Medical Genetics)
Source: BMC Medical Genetics - May 7, 2020 Category: Genetics & Stem Cells Authors: Dulika Sumathipala, Petter Str ømme, Christian Gilissen, Ingunn Holm Einarsen, Hilde J. Bjørndalen, Andrés Server, Jordi Corominas, Bjørnar Hassel, Madeleine Fannemel, Doriana Misceo and Eirik Frengen Tags: Case report Source Type: research
A novel variant in C5ORF42 gene is associated with Joubert syndrome.
In this study, we tested a large pedigree with a history of several affected members with JS. At first the proband was sequenced by NGS technique then, confirmed by sanger sequencing method. After this, all available members of the pedigree were subjected to molecular analysis by sanger sequencing technique. The results of this study showed a novel variant in the C5ORF42 gene c.3080A > T: p. D1027V leading to a substitution of a valine for aspartic acid (D1027V) and may be associated with JS. This variant was present in proband compatible with autosomal recessive pattern. Also this variant was present in all parents...
Source: Molecular Biology Reports - May 3, 2020 Category: Molecular Biology Authors: Mardani R, Taghizadeh E, Taheri F, Raeisi M, Karimzadeh MR, Rostami D, Ferns GA, Ghayour-Mobarhan M Tags: Mol Biol Rep Source Type: research
Four novel compound heterozygous mutations in C5orf42 gene in patients with pure and mild Joubert syndrome.
Abstract
Joubert syndrome (JS) is a rare clinically and genetically heterogeneous disease. Using whole or targeted exome sequencing, we identified four novel compound heterozygous mutations in chromosome 5 open reading frame 42 gene (C5orf42), including c.2876C>T (missense mutation) and c.3921+1G>A (splicing mutation), c.2292 -2delA (splicing mutation) and c.4067C>T (missense mutation), c.6997_6998insT (frameshift mutation) and c.8710C>T (nonsense mutation), c.3981G>C (nonsense mutation) and c.230 _233del (frameshift mutation), in four Chinese JS families. They were all inherited from their ...
Source: International Journal of Developmental Neuroscience - March 30, 2020 Category: Neuroscience Authors: Liu Q, Wang H, Zhao J, Liu Z, Sun D, Yuan A, Luo G, Wei W, Hou M Tags: Int J Dev Neurosci Source Type: research
Copy number variations and multiallelic variants in Korean patients with Leber congenital amaurosis.
Conclusions: This study demonstrated that approximately 4% of patients may have dual molecular diagnoses, and 6% were surgically or medically actionable in LCA. Therefore, accurate molecular diagnosis and careful interpretation of next-generation sequencing results can be of great help in patients with LCA.
PMID: 32165824 [PubMed - in process] (Source: Molecular Vision)
Source: Molecular Vision - March 15, 2020 Category: Molecular Biology Tags: Mol Vis Source Type: research
Co-occurrence of mutations in KIF7 and KIAA0556 in Joubert syndrome with ocular coloboma, pituitary malformation and growth hormone deficiency: a case report and literature review
Joubert syndrome is a recessive neurodevelopmental disorder characterized by clinical and genetic heterogeneity. Clinical hallmarks include hypotonia, ataxia, facial dysmorphism, abnormal eye movement, irregul... (Source: BMC Pediatrics)
Source: BMC Pediatrics - March 12, 2020 Category: Pediatrics Authors: Marcello Niceta, Maria Lisa Dentici, Andrea Ciolfi, Romana Marini, Sabina Barresi, Francesca Romana Lepri, Antonio Novelli, Enrico Bertini, Marco Cappa, Maria Cristina Digilio, Bruno Dallapiccola and Marco Tartaglia Tags: Case report Source Type: research
Optic vesicle morphogenesis requires primary cilia.
Abstract
Arl13b is a gene known to regulate ciliogenesis. Functional alterations in this gene's activity have been associated with Joubert syndrome. We found that in Arl13 null mouse embryos the orientation of the optic cup is inverted, such that the lens is abnormally surrounded by an inverted optic vesicle whose retina pigmented epithelium is oddly facing the surface ectoderm. Loss of Arl13b leads to disruption of optic vesicles patterning and expansion of ventral fates. We show that this phenotype is consequence of miss-regulation of Sonic hedgehog signaling and demonstrate that the Arl13b-/- eye phenot...
Source: Developmental Biology - March 9, 2020 Category: Biology Authors: Fiore L, Takata N, Acosta S, Ma W, Pandit T, Oxendine M, Oliver G Tags: Dev Biol Source Type: research
