The expanding phenotype of OFD1 ‐related disorders: Hemizygous loss‐of‐function variants in three patients with primary ciliary dyskinesia
ConclusionAs clinicians consider the presence or absence of conditions allelic atOFD1, PCD should be considered part of the spectrum ofOFD1‐related disorders. Understanding theOFD1‐related disease spectrum may allow for more focused genetic testing and more timely management of treatable sequelae. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - July 31, 2019 Category: Genetics & Stem Cells Authors: William B. Hannah,
Suzanne DeBrosse,
BreAnna Kinghorn,
Steven Strausbaugh,
Moira L. Aitken,
Margaret Rosenfeld,
Whitney E. Wolf,
Michael R. Knowles,
Maimoona A. Zariwala Tags: ORIGINAL ARTICLE Source Type: research
TALPID3 in Joubert syndrome and related ciliopathy disorders.
Abstract
TALPID3 (KIAA0586) is a centrosomal protein which has specific functions during centriole maturation during the formation of the centrosomal-dependent organelle, the cilia, as well as less well understood roles in the cytoskeleton and during cell polarisation. Cilia are an essential component of signal transduction during embryonic development and the loss of TALPID3 function in humans can cause both severe lethal and mild cilia-related developmental disorders known as 'ciliopathies' the most common being Joubert syndrome. TALPID3 related ciliopathies affect the development of multiple organ syste...
Source: Current Opinion in Genetics and Development - July 17, 2019 Category: Genetics & Stem Cells Authors: Fraser AM, Davey MG Tags: Curr Opin Genet Dev Source Type: research
Identification of a new homozygous CEP290 gene mutation in a Saudi Family causing joubert syndrome using next-generation sequencing.
Abstract
A 19-year-old female with a learning difficulty, ataxia, and nystagmus was referred to our clinic with advanced chronic kidney disease. Her renal biopsy revealed features of nephronophthisis (NPHP). Magnetic resonance imaging of the brain showed "molar tooth sign." The clinical picture was consistent with Joubert syndrome (JS). Two of her siblings were subsequently found to have a similar condition. Genomic material from the patient, her twin sister, and later on from parents was analyzed for deletion/duplication mutations in the NPHP1 gene using multiplex ligation-dependent probe amplification. N...
Source: Saudi Journal of Kidney Diseases and Transplantation - June 30, 2019 Category: Urology & Nephrology Authors: Abdelgadir E, Al Sahlawi M, Al Turki L, Khamees K, Ahmed W Tags: Saudi J Kidney Dis Transpl Source Type: research
Production and characterization of human induced pluripotent stem cells (iPSC) CSSi007-A (4383) from Joubert Syndrome
Publication date: Available online 5 June 2019Source: Stem Cell ResearchAuthor(s): Filomena Altieri, Angela D'Anzi, Francesco Martello, Silvia Tardivo, Iolanda Spasari, Daniela Ferrari, Laura Bernardini, Giuseppe Lamorte, Gianluigi Mazzoccoli, Enza Maria Valente, Angelo Luigi Vescovi, Jessica RosatiAbstractJoubert syndrome (JS) is an autosomal recessive neurodevelopmental disorder, characterized by congenital cerebellar and brainstem defects, belonging to the group of disorders known as ciliopathies, which are caused by mutations in genes encoding proteins of the primary cilium and basal body. Human induced pluripotent ste...
Source: Stem Cell Research - June 5, 2019 Category: Stem Cells Source Type: research
Gene mutation and clinical analysis of nephronophthisis diagnosed using whole exome sequencing: Experience from China
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CONCLUSION: Whole exome sequencing identified the causative genes of NPH in 5 children. In NPH children with NPHP3 gene mutations, renal functional damage was characterized by early onset and rapid progression to ESRD, often accompanied by liver dysfunction and hypertension.
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PMID: 31131822 [PubMed - as supplied by publisher] (Source: Clinical Nephrology)
Source: Clinical Nephrology - May 26, 2019 Category: Urology & Nephrology Authors: Tang X, Xu H, Shen Q, Li G, Rao J, Chen J, Zhai Y, Miao Q Tags: Clin Nephrol Source Type: research
A Child with Joubert Syndrome: Clinical and Imaging Features.
Authors: Abri Aghdam K, Zand A, Sanjari MS
PMID: 31114663 [PubMed] (Source: Journal of Ophthalmic and Vision Research)
Source: Journal of Ophthalmic and Vision Research - May 24, 2019 Category: Opthalmology Tags: J Ophthalmic Vis Res Source Type: research
Overlap of polymicrogyria, hydrocephalus, and Joubert syndrome in a family with novel truncating mutations in ADGRG1/GPR56 and KIAA0556
This study shows how two independent mutations can interact leading to complex brain malformations. (Source: Neurogenetics)
Source: Neurogenetics - April 12, 2019 Category: Genetics & Stem Cells Source Type: research
Bi-allelic Mutations in FAM149B1 Cause Abnormal Primary Cilium and a Range of Ciliopathy Phenotypes in Humans
Ciliopathies are clinical disorders of the primary cilium with widely recognized phenotypic and genetic heterogeneity. In two Arab consanguineous families, we mapped a ciliopathy phenotype that most closely matches Joubert syndrome (hypotonia, developmental delay, typical facies, oculomotor apraxia, polydactyly, and subtle posterior fossa abnormalities) to a single locus in which a founder homozygous truncating variant in FAM149B1 was identified by exome sequencing. We subsequently identified a third Arab consanguineous multiplex family in which the phenotype of Joubert syndrome/oral-facial-digital syndrome (OFD VI) was fo...
Source: The American Journal of Human Genetics - March 20, 2019 Category: Genetics & Stem Cells Authors: Ranad Shaheen, Nan Jiang, Fatema Alzahrani, Nour Ewida, Tarfa Al-Sheddi, Eman Alobeid, Damir Musaev, Valentina Stanley, Mais Hashem, Niema Ibrahim, Firdous Abdulwahab, Abduljabbar Alshenqiti, Fatma Mujgan Sonmez, Nadia Saqati, Hamad Alzaidan, Mohammad M. Tags: Report Source Type: research
Joubert Syndrome: Two Different Prenatal Ultrasound Presentations
AbstractJoubert syndrome is a rare brainstem malformation characterized by hypoplastic vermis, thickened and elongated superior cerebellar peduncles, abnormally shaped 4th ventricle which may be associated with renal, ocular, hepatic orodigitofacial and cranial abnormalities and can be diagnosed on prenatal ultrasound and now is considered a part of Joubert syndrome and related syndromes (JSRD). Two prenatally detected cases of JSRD presented here expand the spectrum of sonological signs which should prompt a fetal medicine specialist to suspect JSRD. (Source: Journal of Fetal Medicine)
Source: Journal of Fetal Medicine - February 26, 2019 Category: Perinatology & Neonatology Source Type: research
The Frog Xenopus as a Model to Study Joubert Syndrome: The Case of a Human Patient With Compound Heterozygous Variants in PIBF1
Tim Ott, Lilian Kaufmann, Martin Granzow, Katrin Hinderhofer, Claus R. Bartram, Susanne Thei ß, Angelika Seitz, Nagarajan Paramasivam, Angela Schulz, Ute Moog, Martin Blum, Christina M. Evers (Source: Frontiers in Physiology)
Source: Frontiers in Physiology - February 25, 2019 Category: Physiology Source Type: research
Phosphoinositides in the kidney [Thematic Reviews]
Phosphoinositides (PIs) play pivotal roles in the regulation of many biological processes. The quality and quantity of PIs is regulated in time and space by the activity of PI kinases and PI phosphatases. The number of PI-metabolizing enzymes exceeds the number of PIs with, in many cases, more than one enzyme controlling the same biochemical step. This would suggest that the PI system has an intrinsic ability to buffer and compensate for the absence of a specific enzymatic activity. However, there are several examples of severe inherited human diseases caused by mutations in one of the PI enzymes, although other enzymes wi...
Source: The Journal of Lipid Research - February 1, 2019 Category: Lipidology Authors: Staiano, L., De Matteis, M. A. Tags: Thematic Reviews Source Type: research
Targeted exon skipping of a CEP290 mutation rescues Joubert syndrome phenotypes in vitro and in a murine model [Medical Sciences]
Genetic treatments of renal ciliopathies leading to cystic kidney disease would provide a real advance in current therapies. Mutations in CEP290 underlie a ciliopathy called Joubert syndrome (JBTS). Human disease phenotypes include cerebral, retinal, and renal disease, which typically progresses to end stage renal failure (ESRF) within the first two... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - December 4, 2018 Category: Science Authors: Simon A. Ramsbottom, Elisa Molinari, Shalabh Srivastava, Flora Silberman, Charline Henry, Sumaya Alkanderi, Laura A. Devlin, Kathryn White, David H. Steel, Sophie Saunier, Colin G. Miles, John A. Sayer Tags: Biological Sciences Source Type: research
Genes, Vol. 9, Pages 605: Review of Ocular Manifestations of Joubert Syndrome
In conclusion, Joubert syndrome is a rare pleiotropic group of disorders with variable ocular presentations. (Source: Genes)
Source: Genes - December 4, 2018 Category: Genetics & Stem Cells Authors: Stephanie F. Wang Tia J. Kowal Ke Ning Euna B. Koo Albert Y. Wu Vinit B. Mahajan Yang Sun Tags: Review Source Type: research
Proteins that control the geometry of microtubules at the ends of cilia
Cilia, essential motile and sensory organelles, have several compartments: the basal body, transition zone, and the middle and distal axoneme segments. The distal segment accommodates key functions, including cilium assembly and sensory activities. While the middle segment contains doublet microtubules (incomplete B-tubules fused to complete A-tubules), the distal segment contains only A-tubule extensions, and its existence requires coordination of microtubule length at the nanometer scale. We show that three conserved proteins, two of which are mutated in the ciliopathy Joubert syndrome, determine the geometry of the dist...
Source: Journal of Cell Biology - December 3, 2018 Category: Cytology Authors: Louka, P., Vasudevan, K. K., Guha, M., Joachimiak, E., Wloga, D., Tomasi, R. F.- X., Baroud, C. N., Dupuis-Williams, P., Galati, D. F., Pearson, C. G., Rice, L. M., Moresco, J. J., Yates, J. R., Jiang, Y.-Y., Lechtreck, K., Dentler, W., Gaertig, J. Tags: Disease, Cytoskeleton, Cilia Articles Source Type: research
A novel PDE6D mutation in a patient with Joubert syndrome type 22 (JBTS22).
Abstract
Joubert syndrome (JS) is an autosomal or X-linked recessive syndrome principally characterized by hypotonia, ataxia, cognitive impairment, and a specific finding on brain imaging called a "molar tooth sign" (MTS), which can be isolated or in conjunction with variable organ involvement. The genetic basis of JS is heterogeneous, with over 35 ciliary genes being implicated in its pathogenesis. However, some of these genes (such as PDE6D) have been associated to JS only in single families, seeking confirmation. Here we report a boy, born to first cousin parents, presenting with developmental delay, hy...
Source: European Journal of Medical Genetics - November 10, 2018 Category: Genetics & Stem Cells Authors: Mégarbané A, Hmaimess G, Bizzari S, El-Bazzal L, Al-Ali MT, Stora S, Delague V, El Hayek S Tags: Eur J Med Genet Source Type: research
