Whole exome sequencing reveals a mutation in ARMC9 as a cause of mental retardation, ptosis, and polydactyly
We report on elucidation of molecular basis for syndromic ID associated with ptosis, polydactyly, and MRI features suggestive of Joubert syndrome using homozygosity mapping followed by exome sequencing. The analysis revealed a novel synonymous variation p.T293T (c.879G>A) which leads to a splicing defect in ARMC9 gene. The variant is present in conserved region of ARM domain of ARMC9 protein, which is predicted to form a platform for protein interaction. This domain is likely to be altered in patient due to splicing defect caused by this synonymous variation. Our report of variant in ARMC9 Leading to Joubert syndrome ph...
Source: American Journal of Medical Genetics Part A - November 21, 2017 Category: Genetics & Stem Cells Authors: Anjana Kar, Shubha R. Phadke, Aneek Das Bhowmik, Ashwin Dalal Tags: ORIGINAL ARTICLE Source Type: research
Prospective Evaluation of Kidney Disease in Joubert Syndrome.
CONCLUSIONS: Kidney disease occurs in up to one third of patients with Joubert syndrome, most commonly in those with mutations in CEP290, TMEM67, and AHI1. Patients with mutations in C5orf42 or KIAA0586 are less likely to develop kidney disease. Prenatal ultrasonography is a poor predictor of kidney involvement in Joubert syndrome. Unilateral multicystic dysplastic kidney and autosomal recessive polycystic kidney disease-like enlarged kidneys with early-onset hypertension can be part of the Joubert syndrome kidney phenotype.
PMID: 29146704 [PubMed - as supplied by publisher] (Source: Clinical Journal of the America...
Source: Clinical Journal of the American Society of Nephrology : CJASN - November 16, 2017 Category: Urology & Nephrology Authors: Fleming LR, Doherty DA, Parisi MA, Glass IA, Bryant J, Fischer R, Turkbey B, Choyke P, Daryanani K, Vemulapalli M, Mullikin JC, Malicdan MC, Vilboux T, Sayer JA, Gahl WA, Gunay-Aygun M Tags: Clin J Am Soc Nephrol Source Type: research
A novel homozygous ARL13B variant in patients with Joubert syndrome impairs its guanine nucleotide-exchange factor activity
A novel homozygous <i>ARL13B</i> variant in patients with Joubert syndrome impairs its guanine nucleotide-exchange factor activity, Published online: 15 November 2017; doi:10.1038/s41431-017-0031-0 (Source: European Journal of Human Genetics)
Source: European Journal of Human Genetics - November 15, 2017 Category: Genetics & Stem Cells Authors: Rafiullah Rafiullah Alyssa B. Long Anna A. Ivanova Hazrat Ali Simone Berkel Ghulam Mustafa Nagarajan Paramasivam Matthias Schlesner Stefan Wiemann Rebecca C. Wade Eugen Bolthauser Martin Blum Richard A. Kahn Tamara Caspary Gudrun A. Rappold Source Type: research
Cover Image, Volume 173A, Number 12, December 2017
The cover image, by Isabel Hardee et al., is based on the Clinical Report Defective ciliogenesis in INPP5E‐related Joubert syndrome, DOI: 10.1002/ajmg.a.38376. Design Credit: Darryl Leja. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - November 14, 2017 Category: Genetics & Stem Cells Authors: Isabel Hardee, Ariane Soldatos, Mariska Davids, Thierry Vilboux, Camilo Toro, Karen L. David, Carlos R. Ferreira, Michele Nehrebecky, Joseph Snow, Audrey Thurm, Theo Heller, Ellen F. Macnamara, Meral Gunay ‐Aygun, Wadih M. Zein, William A. Gahl, May Chr Tags: COVER IMAGE Source Type: research
A Homozygous Missense Variant in < b > < i > INPP5E < /i > < /b > Associated with Joubert Syndrome and Related Disorders
We report a novel homozygous mutation identified in theINPP5E gene, c.1303C>T, which leads to a change of an amino acid from arginine to tryptophan at residue 435 in the protein chain. In silico analysis indicates that p.Arg435Trp substitution affects the functionality of the protein product of the gene. Our result adds to the growing body of evidences that underlines the clinical utility of next-generation sequencing in the diagnosis of a genetic disorder when clinical features are inconclusive.Mol Syndromol 2017;8:313-317 (Source: Molecular Syndromology)
Source: Molecular Syndromology - November 1, 2017 Category: Molecular Biology Source Type: research
Erratum: Super-resolution microscopy reveals that disruption of ciliary transition-zone architecture causes Joubert syndrome
Nature Cell Biology 19, 1379 (2017).
doi:10.1038/ncb3622
Author: Xiaoyu Shi, Galo Garcia, Julie C. Van De Weghe, Ryan McGorty, Gregory J. Pazour, Dan Doherty, Bo Huang & Jeremy F. Reiter (Source: Nature Cell Biology)
Source: Nature Cell Biology - October 31, 2017 Category: Cytology Authors: Xiaoyu Shi Galo Garcia Julie C. Van De Weghe Ryan McGorty Gregory J. Pazour Dan Doherty Bo Huang Jeremy F. Reiter Tags: Erratum Source Type: research
Decaying molar tooth sign in Joubert syndrome and related disorders is correlated to a displacement of the corticospinal tract
(Source: Neuroradiology)
Source: Neuroradiology - October 28, 2017 Category: Radiology Source Type: research
A Homozygous Missense Variant in INPP5E Associated with Joubert Syndrome and Related Disorders
We report a novel homozygous mutation identified in theINPP5E gene, c.1303C>T, which leads to a change of an amino acid from arginine to tryptophan at residue 435 in the protein chain. In silico analysis indicates that p.Arg435Trp substitution affects the functionality of the protein product of the gene. Our result adds to the growing body of evidences that underlines the clinical utility of next-generation sequencing in the diagnosis of a genetic disorder when clinical features are inconclusive.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - October 25, 2017 Category: Molecular Biology Source Type: research
Defective ciliogenesis in INPP5E ‐related Joubert syndrome
Joubert syndrome is a neurodevelopmental disorder, characterized by malformation of the mid and hindbrain leading to the pathognomonic molar tooth appearance of the brainstem and cerebellum on axial MRI. Core clinical manifestations include hypotonia, tachypnea/apnea, ataxia, ocular motor apraxia, and developmental delay of varying degrees. In addition, a subset of patients has retinal dystrophy, chorioretinal colobomas, hepatorenal fibrocystic disease, and polydactyly. Joubert syndrome exhibits genetic heterogeneity, with mutations identified in more than 30 genes, including INPP5E, a gene encoding inositol polyphosphate ...
Source: American Journal of Medical Genetics Part A - October 1, 2017 Category: Genetics & Stem Cells Authors: Isabel Hardee, Ariane Soldatos, Mariska Davids, Thierry Vilboux, Camilo Toro, Karen L. David, Carlos R. Ferreira, Michele Nehrebecky, Joseph Snow, Audrey Thurm, Theo Heller, Ellen F. Macnamara, Meral Gunay ‐Aygun, Wadih M. Zein, William A. Gahl, May Chr Tags: CLINICAL REPORT Source Type: research
Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedgehog Pathway and Cause Joubert Syndrome with Cranio-facial and Skeletal Defects
The Sonic Hedgehog (SHH) pathway is a key signaling pathway orchestrating embryonic development, mainly of the CNS and limbs. In vertebrates, SHH signaling is mediated by the primary cilium, and genetic defects affecting either SHH pathway members or ciliary proteins cause a spectrum of developmental disorders. SUFU is the main negative regulator of the SHH pathway and is essential during development. Indeed, Sufu knock-out is lethal in mice, and recessive pathogenic variants of this gene have never been reported in humans. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - September 28, 2017 Category: Genetics & Stem Cells Authors: Roberta De Mori, Marta Romani, Stefano D ’Arrigo, Maha S. Zaki, Elisa Lorefice, Silvia Tardivo, Tommaso Biagini, Valentina Stanley, Damir Musaev, Joel Fluss, Alessia Micalizzi, Sara Nuovo, Barbara Illi, Luisa Chiapparini, Lucia Di Marcotullio, Mahmoud Y Tags: Article Source Type: research
A Homozygous Missense Variant in INPP5E Associated with Joubert Syndrome and Related Disorders
We report a novel homozygous mutation identified in theINPP5E gene, c.1303C>T, which leads to a change of an amino acid from arginine to tryptophan at residue 435 in the protein chain. In silico analysis indicates that p.Arg435Trp substitution affects the functionality of the protein product of the gene. Our result adds to the growing body of evidences that underlines the clinical utility of next-generation sequencing in the diagnosis of a genetic disorder when clinical features are inconclusive.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - September 8, 2017 Category: Molecular Biology Source Type: research
A Homozygous Missense Variant in < b > < i > INPP5E < /i > < /b > Associated with Joubert Syndrome and Related Disorders
We report a novel homozygous mutation identified in theINPP5E gene, c.1303C>T, which leads to a change of an amino acid from arginine to tryptophan at residue 435 in the protein chain. In silico analysis indicates that p.Arg435Trp substitution affects the functionality of the protein product of the gene. Our result adds to the growing body of evidences that underlines the clinical utility of next-generation sequencing in the diagnosis of a genetic disorder when clinical features are inconclusive.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - September 7, 2017 Category: Molecular Biology Source Type: research
Uniparental disomy as an unexpected cause of Meckel –Gruber syndrome: report of a case
ConclusionsThis is the first reported case of UPD as a cause of MKS. The possible underlying mechanisms for uniparental disomy (UPD) are reviewed. Even if rare, awareness of UPD and comprehensive work-up in the case of unexpected homozygosity for a recessive mutation is essential for accurate genetic counseling and assessment of the risk of recurrence. (Source: Pediatric Nephrology)
Source: Pediatric Nephrology - August 31, 2017 Category: Urology & Nephrology Source Type: research
Joubert Syndrome Associated with Seizures.
Authors: Mugundhan K, Mayan MCV, Nidhin PD, Loganathan G, Balamurugan N
PMID: 28799313 [PubMed - in process] (Source: Journal of the Association of Physicians of India)
Source: Journal of the Association of Physicians of India - August 13, 2017 Category: General Medicine Tags: J Assoc Physicians India Source Type: research
Molecular genetic findings and clinical correlations in 100 patients with Joubert syndrome and related disorders prospectively evaluated at a single center
uencing Program, May Christine V. Malicdan, William A. Gahl & Meral Gunay-Aygun (Source: Genetics in Medicine)
Source: Genetics in Medicine - August 4, 2017 Category: Genetics & Stem Cells Authors: Thierry Vilboux Daniel A. Doherty Ian A. Glass Melissa A. Parisi Ian G. Phelps Andrew R. Cullinane Wadih Zein Brian P. Brooks Theo Heller Ariane Soldatos Neal L. Oden Deniz Yildirimli Meghana Vemulapalli James C. Mullikin NISC Comparative Sequencing Prog Tags: ciliopathy clinical and molecular diagnosis Joubert syndrome next-generation sequencing Source Type: research
