Lingual Frenectomy in Joubert Syndrome.
CONCLUSION: The patient treated by us did not reveal any significant intraoperative or postoperative complications. Treatment of cases of JS required a team effort of multiple dental and medical specialists. Long-term follow-up of such patients is required so that they achieve normal chronological development.
CLINICAL SIGNIFICANCE: Joubert syndrome being a rare disorder requires special anesthetic care during any surgical procedure, especially that involving the oral cavity. The need and timing of surgical intervention in such cases should be carefully assessed and appropriate precautions should be taken.
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Source: J Contemp Dent Pract - August 1, 2017 Category: Dentistry Authors: Gurjar V, Gurjar M, Pattanshetti C, Sankeshwari B Tags: J Contemp Dent Pract Source Type: research
A Common Ancestral Asn242Ser Mutation in TMEM67 Identified in Multiple Iranian Families with Joubert Syndrome
Conclusion: We propose that Asn242Ser is a founder mutation in the Iranian population, which might explain a significant proportion of JS cases from eastern Iran. Therefore, screening for this variant should be considered for genetic testing in Iranian patients with JS. In addition, this finding is important for developing population-specific genetic testing in Iran.Public Health Genomics (Source: Public Health Genomics)
Source: Public Health Genomics - July 19, 2017 Category: Genetics & Stem Cells Source Type: research
A Common Ancestral Asn242Ser Mutation in < b > < i > TMEM67 < /i > < /b > Identified in Multiple Iranian Families with Joubert Syndrome
Conclusion: We propose that Asn242Ser is a founder mutation in the Iranian population, which might explain a significant proportion of JS cases from eastern Iran. Therefore, screening for this variant should be considered for genetic testing in Iranian patients with JS. In addition, this finding is important for developing population-specific genetic testing in Iran.Public Health Genomics (Source: Public Health Genomics)
Source: Public Health Genomics - July 18, 2017 Category: Genetics & Stem Cells Source Type: research
In Vitro Modeling Using Ciliopathy-Patient-Derived Cells Reveals Distinct Cilia Dysfunctions Caused by CEP290 Mutations
We examined cilia biogenesis and function in cells derived from CEP290-LCA and CEP290-JSRD patients. CEP290 protein was reduced in LCA fibroblasts with no detectable impact on cilia; however, optic cups derived from induced pluripotent stem cells (iPSCs) of CEP290-LCA patients displayed less developed photoreceptor cilia. Lack of CEP290 in JSRD fibroblasts resulted in abnormal cilia and decreased ciliogenesis. We observed selectively reduced localization of ADCY3 and ARL13B. Notably, Hedgehog signaling was augmented in CEP290-JSRD because of enhanced ciliary transport of Smoothened and GPR161. These results demonstrate a d...
Source: Cell Reports - July 12, 2017 Category: Cytology Source Type: research
This Month in The Journal
Joubert syndrome (JS) is a ciliopathy characterized by hypotonia, ataxia, and a “molar tooth sign” on MRI, and it can also involve cognitive defects. This genetically heterogeneous disorder is caused by mutations in more than three dozen genes that encode proteins required for cilia formation or function. In this issue, Van de Weghe et al. identify ARMC9 mutations in eigh t JS-affected families in whom mutations in previously associated genes had already been ruled. The families were ascertained through different mechanisms, but the combined cohort data suggest that ARMC9 mutations might explain the genetic defect in...
Source: The American Journal of Human Genetics - July 6, 2017 Category: Genetics & Stem Cells Authors: Sarah Ratzel, Sara B. Cullinan Tags: Editors' Corner Source Type: research
Biochemical characterization of purified mammalian ARL13B protein indicates that it is an atypical GTPase and ARL3 guanine nucleotide exchange factor (GEF) [Enzymology]
We report results from assays for solution-based nucleotide binding, intrinsic and GTPase-activating protein-stimulated GTPase, and ARL3 guanine nucleotide exchange factor activities. Biochemical analyses of three human missense mutations found in JS and of two consensus GTPase motifs reinforce the atypical properties of this regulatory GTPase. We also discovered that murine Arl13b is a substrate for casein kinase 2, a contaminant in our preparation from human embryonic kidney cells. This activity, and the ability of casein kinase 2 to use GTP as a phosphate donor, may be a source of differences between our data and previo...
Source: Journal of Biological Chemistry - June 30, 2017 Category: Chemistry Authors: Anna A. Ivanova, Tamara Caspary, Nicholas T. Seyfried, Duc M. Duong, Andrew B. West, Zhiyong Liu, Richard A. Kahn Tags: Signal Transduction Source Type: research
Expanding the allelic disorders linked to TCTN1 to include Varadi syndrome (Orofaciodigital syndrome type VI)
In this report, we describe the phenotype of a patient with Varadi syndrome who is homozygous for a previously reported mutation in TCTN1 (NM_001082538.2:c.342‐2A>G, p.Gly115Lysfs*8) and suggest that allelic disorders linked to TCTN1 include Varadi syndrome, in addition to Joubert syndrome and Meckel–Gruber syndrome. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - June 20, 2017 Category: Genetics & Stem Cells Authors: Mohammad M. Al ‐Qattan, Ranad Shaheen, Fowzan S. Alkuraya Tags: RESEARCH LETTER Source Type: research
Mutations in ARMC9, which Encodes a Basal Body Protein, Cause Joubert Syndrome in Humans and Ciliopathy Phenotypes in Zebrafish
Joubert syndrome (JS) is a recessive neurodevelopmental disorder characterized by hypotonia, ataxia, abnormal eye movements, and variable cognitive impairment. It is defined by a distinctive brain malformation known as the “molar tooth sign” on axial MRI. Subsets of affected individuals have malformations such as coloboma, polydactyly, and encephalocele, as well as progressive retinal dystrophy, fibrocystic kidney disease, and liver fibrosis. More than 35 genes have been associated with JS, but in a subset of fami lies the genetic cause remains unknown. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - June 15, 2017 Category: Genetics & Stem Cells Authors: Julie C. Van De Weghe, Tamara D.S. Rusterholz, Brooke Latour, Megan E. Grout, Kimberly A. Aldinger, Ranad Shaheen, Jennifer C. Dempsey, Sateesh Maddirevula, Yong-Han H. Cheng, Ian G. Phelps, Matthias Gesemann, Himanshu Goel, Ohad S. Birk, Talal Alanzi, Ri Tags: Article Source Type: research
Novel OFD1 frameshift mutation in a Chinese boy with Joubert syndrome: a case report and literature review
In this study, we identified a novel OFD1 mutation of c.2843_2844 delAA (p.Lys948ArgfsX) in a 3-month-old boy with a ‘molar tooth sign’ and clinical features of JBTS using targeted exome next-generation sequencing. The de-novo OFD1 mutation in exon 21 leads to a frameshift mutation generating a prematurely truncated protein and is predicted to partly reduce the function of the OFD1 protein. Our study expands the genotype–phenotype spectrum in JBTS and will have applications in prenatal and early diagnosis of the disorder. This is the first report of the OFD1 mutation causing JBTS in a Chinese population. (Source: Clinical Dysmorphology)
Source: Clinical Dysmorphology - June 6, 2017 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Prenatal diagnosis of Joubert syndrome by ultrasound and magnetic resonance imaging – report of three cases
Three pregnant women were detected with their fetuses showing abnormalities in the mid-hindbrain by prenatal ultrasound and magnetic resonance imaging (MRI) examination. The “molar tooth sign” appeared between the superior cerebellar peduncle and the midbrain. These fetuses were all diagnosed with Joubert syndrome with MRI. The diagnosis of Joubert syndrome during pregnancy is very rare. MRI examination during pregnancy is very important for the diagnosis of Joubert syndrome. The “molar tooth sign” and the crevice between the hemispherium cerebelli can be used for early detection of Joubert syndrome. (Source: Taiwa...
Source: Taiwanese Journal of Obstetrics and Gynecology - June 1, 2017 Category: OBGYN Authors: Xudong Yu, Zhong Zhen, Juanxia Li, Wenzhong Yang, Xinlin Chen Tags: Research Letter Source Type: research
Fundus findings in a case of Joubert syndrome
Rohan Chawla, Ravi Bypareddy, Laxman Vekaria, Pradeep Venkatesh, Venkatesh Hosur AnanthashayanaIndian Journal of Ophthalmology 2017 65(4):329-330 (Source: Indian Journal of Ophthalmology)
Source: Indian Journal of Ophthalmology - May 17, 2017 Category: Opthalmology Authors: Rohan Chawla Ravi Bypareddy Laxman Vekaria Pradeep Venkatesh Venkatesh Hosur Ananthashayana Source Type: research
Neuropsychological phenotypes of 76 individuals with Joubert syndrome evaluated at a single center
Joubert syndrome (JS) is a genetically heterogeneous ciliopathy characterized by hypo‐dysplasia of the cerebellar vermis, a distinct hindbrain/midbrain malformation (molar tooth sign), and intellectual disability. We evaluated the neuropsychological profiles of 76 participants with JS in the context of molecular genetics and clinical covariates. Evaluations included neuropsychological testing, structured parental interviews, DNA sequencing, brain magnetic resonance imaging (MRI), electroencephalography (EEG), ophthalmologic examination, and assessment for renal and hepatic disease. On average, participants manifested Ful...
Source: American Journal of Medical Genetics Part A - May 12, 2017 Category: Genetics & Stem Cells Authors: Angela C. Summers, Joseph Snow, Edythe Wiggs, Alexander G. Liu, Camilo Toro, Andrea Poretti, Wadih M. Zein, Brian P. Brooks, Melissa A. Parisi, Sara Inati, Dan Doherty, Meghana Vemulapalli, Jim C. Mullikin, , Thierry Vilboux, William A. Gahl, Meral Gunay Tags: ORIGINAL ARTICLE Source Type: research
Identification of 2 Potentially Relevant Gene Mutations Involved in Strabismus Using Whole-Exome Sequencing.
CONCLUSIONS We detected an AHI1 homozygous mutation in the affected individual. Whole-exome sequencing is a powerful way to identify causally relevant genes, improving the understanding of this disorder.
PMID: 28391287 [PubMed - in process] (Source: Medical Science Monitor)
Source: Medical Science Monitor - April 11, 2017 Category: Research Tags: Med Sci Monit Source Type: research
Marshall M. Parks Memorial Lecture: Ocular Motor Misbehavior in Children
Clinical diagnosis has been supplemented by neuroimaging advances, genetic discoveries, and molecular research to generate new neurobiological discoveries pertaining to early maldevelopment of ocular motor control systems. In this focused review, I examine recent paradigm shifts that have transformed our understanding of pediatric ocular motor disease at the prenuclear and infranuclear levels. The pathogenesis of complex ocular motor disorders, such as paradoxical pupillary constriction to darkness, benign tonic upgaze of infancy, congenital fibrosis syndrome, and the constellation of unique eye movements that accompany Jo...
Source: Ophthalmology - April 3, 2017 Category: Opthalmology Authors: Michael C. Brodsky Source Type: research
Mortality in Joubert syndrome
Joubert syndrome (JS) is a rare, recessively inherited neurodevelopmental disorder characterized by a distinctive mid‐hindbrain malformation. Little is known about mortality in affected individuals. Identifying the timing and causes of death will allow for development of healthcare guidelines for families and providers and, thus, help to prolong and improve the lives of patients with JS. We evaluated information on 40 deceased individuals with JS to characterize age and cause of death. We compared this population with 525 living individuals with JS to estimate associations between risk of death and extra‐neurological f...
Source: American Journal of Medical Genetics Part A - March 28, 2017 Category: Genetics & Stem Cells Authors: Jennifer C. Dempsey, Ian G. Phelps, Ruxandra Bachmann ‐Gagescu, Ian A. Glass, Hannah M. Tully, Dan Doherty Tags: ORIGINAL ARTICLE Source Type: research
