Clinical and molecular diagnosis of Joubert syndrome and related disorders
We present a large cohort of 59 patients with JS from 55 families. Molecular analysis was performed in 35 families (trio). (Source: Pediatric Neurology)
Source: Pediatric Neurology - February 2, 2020 Category: Neurology Authors: Akella Radha Rama Devi, Shaik Mohammad Naushad, Lokesh Lingappa Tags: Research Paper Source Type: research
Novel compound heterozygous TMEM67 variants in a Vietnamese family with Joubert syndrome: a case report
Joubert syndrome is a genetically heterogeneous autosomal recessive ciliopathy characterized by the combination of hypoplasia/aplasia of the cerebellar vermis, thickened and elongated superior cerebellar pedun... (Source: BMC Medical Genetics)
Source: BMC Medical Genetics - January 30, 2020 Category: Genetics & Stem Cells Authors: Thi Phuong Hoa Bui, Ngoc Tu Nguyen, Van Doan Ngo, Hoai-Nghia Nguyen, Thi Thanh Ha Ly, Huy Duong Do and Minh-Tuan Huynh Tags: Case report Source Type: research
Mouse genetics reveals Barttin as a genetic modifier of Joubert syndrome [Genetics]
Genetic and phenotypic heterogeneity and the lack of sufficiently large patient cohorts pose a significant challenge to understanding genetic associations in rare disease. Here we identify Bsnd (alias Barttin) as a genetic modifier of cystic kidney disease in Joubert syndrome, using a Cep290-deficient mouse model to recapitulate the phenotypic variability... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - January 13, 2020 Category: Science Authors: Simon A. Ramsbottom, Peter E. Thelwall, Katrina M. Wood, Gavin J. Clowry, Laura A. Devlin, Flora Silbermann, Helena L. Spiewak, Shirlee Shril, Elisa Molinari, Friedhelm Hildebrandt, Meral Gunay-Aygun, Sophie Saunier, Heather J. Cordell, John A. Sayer, Col Tags: Biological Sciences Source Type: research
The Dynamic and Complex Role of the Joubert Syndrome-Associated Ciliary Protein, ADP-Ribosylation Factor-Like GTPase 13B (ARL13B) in Photoreceptor Development and Maintenance.
The Dynamic and Complex Role of the Joubert Syndrome-Associated Ciliary Protein, ADP-Ribosylation Factor-Like GTPase 13B (ARL13B) in Photoreceptor Development and Maintenance.
Adv Exp Med Biol. 2019;1185:501-505
Authors: Dilan T, Ramamurthy V
Abstract
Photoreceptor neurons are modified primary cilia with an extended ciliary compartment known as the outer segment (OS). The mechanism behind the elaboration of photoreceptor cilia and OS morphogenesis remains poorly understood. In this review, we discuss the role of ADP-ribosylation factor-like GTPase 13B (ARL13B), a small GTPase in ...
Source: Advances in Experimental Medicine and Biology - December 31, 2019 Category: Research Tags: Adv Exp Med Biol Source Type: research
Hemi-seesaw nystagmus in Joubert syndrome.
PMID: 31856927 [PubMed - as supplied by publisher] (Source: The Canadian Journal of Neurological Sciences)
Source: The Canadian Journal of Neurological Sciences - December 19, 2019 Category: Neurology Authors: Jang SH, Choi SY, Jeon H, Choi HY, Oh EH, Choi JH, Choi KD Tags: Can J Neurol Sci Source Type: research
Primary Cilia Signaling Promotes Axonal Tract Development and Is Disrupted in Joubert Syndrome-Related Disorders Models.
Abstract
Appropriate axonal growth and connectivity are essential for functional wiring of the brain. Joubert syndrome-related disorders (JSRD), a group of ciliopathies in which mutations disrupt primary cilia function, are characterized by axonal tract malformations. However, little is known about how cilia-driven signaling regulates axonal growth and connectivity. We demonstrate that the deletion of related JSRD genes, Arl13b and Inpp5e, in projection neurons leads to de-fasciculated and misoriented axonal tracts. Arl13b deletion disrupts the function of its downstream effector, Inpp5e, and deregulates ...
Source: Developmental Cell - December 15, 2019 Category: Cytology Authors: Guo J, Otis JM, Suciu SK, Catalano C, Xing L, Constable S, Wachten D, Gupton S, Lee J, Lee A, Blackley KH, Ptacek T, Simon JM, Schurmans S, Stuber GD, Caspary T, Anton ES Tags: Dev Cell Source Type: research
Atypical, milder presentation in a child with CC2D2A and KIDINS220 variants
With the increasing availability and clinical use of exome and whole-genome sequencing, reverse phenotyping is now becoming common practice in clinical genetics. Here, we report a patient identified through the Wellcome Trust Deciphering Developmental Disorders study who has homozygous pathogenic variants in CC2D2A and a de-novo heterozygous pathogenic variant in KIDINS220. He presents with developmental delay, intellectual disability, and oculomotor apraxia. Reverse phenotyping has demonstrated that he likely has a composite phenotype with contributions from both variants. The patient is much more mildly affected than tho...
Source: Clinical Dysmorphology - December 6, 2019 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
A new case of KIAA0753-related variant of Jeune asphyxiating thoracic dystrophy.
We present the clinical characteristics of a eighth such patient. This 4 year-old boy with narrow thorax, short limbs, severe respiratory and feeding difficulties from birth on had a history of hypotonia and developmental delay. On skeletal survey, short tubular bones (height - 5,5 SD) and a trident appearance of the pelvis were seen. Brain MRI showed cervical canal stenosis. Renal function was normal and moderate hepatomegaly was noted. A homozygous c.943C > T mutation in KIAA0753 was identified on whole exome sequencing, resulting in Gln315Ter premature termination of the corresponding protein. This case provides ...
Source: European Journal of Medical Genetics - December 5, 2019 Category: Genetics & Stem Cells Authors: Faudi E, Brischoux-Boucher E, Huber C, Dabudyk T, Lenoir M, Baujat G, Michot C, Van Maldergem L, Cormier-Daire V, Piard J Tags: Eur J Med Genet Source Type: research
The Fetal Posterior Fossa on Prenatal Ultrasound Imaging: Normal Longitudinal Development and Posterior Fossa Anomalies.
Abstract
Fetal neurosonography and the assessment of the posterior fossa have gained in importance during the last 2 decades primarily due to the development of high-resolution ultrasound probes and the introduction of 3 D sonography. The anatomical development of the posterior fossa can be visualized well with the newest ultrasound technologies. This allows better knowledge of the anatomical structures and helps with understanding of the development of malformations of the posterior fossa. In this article the longitudinal development of the posterior fossa structures will be reviewed. The embryologic de...
Source: Ultraschall in der Medizin - November 30, 2019 Category: Radiology Authors: Pertl B, Eder S, Stern C, Verheyen S Tags: Ultraschall Med Source Type: research
Whole exome sequencing reveals novel CEP104 mutations in a Chinese patient with Joubert syndrome
ConclusionOur study reported the fourth case of JS patients withCEP104 mutations, which expands the mutation spectrum ofCEP104 and elucidates the clinical heterogeneity of JS. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - October 17, 2019 Category: Genetics & Stem Cells Authors: Minna Luo,
Li Cao,
Zongfu Cao,
Siyu Ma,
Yue Shen,
Di Yang,
Chao Lu,
Zaisheng Lin,
Zhimin Liu,
Yufei Yu,
Ruikun Cai,
Cuixia Chen,
Huafang Gao,
Xueyan Wang,
Muqing Cao,
Xu Ma Tags: ORIGINAL ARTICLE Source Type: research
Diagnosis of Congenital Hepatic Fibrosis in Adulthood.
CONCLUSIONS: While other disease associations and characteristic liver histomorphology are helpful clues to suspect the diagnosis of CHF in adult patients, other differential diagnoses should be excluded clinically and radiologically. This study highlights the importance of a multidisciplinary diagnostic approach by pathologists, radiologists, and hepatologists for the accurate diagnosis of CHF during adulthood.
PMID: 31584623 [PubMed - as supplied by publisher] (Source: American Journal of Clinical Pathology)
Source: American Journal of Clinical Pathology - October 3, 2019 Category: Pathology Authors: Alsomali MI, Yearsley MM, Levin DM, Chen W Tags: Am J Clin Pathol Source Type: research
DNA Variant in the < b > < i > RPGRIP1L < /i > < /b > Gene Influences Alternative Splicing
In this study we identify a common variant inRPGRIP1L, rs7203525, that influences alternative splicing, increasing the inclusion of exon 20 ofRPGRIP1L. We detected this alternative splicing association in human postmortem brain tissue samples and, using a minigene assay combined with in vitro mutagenesis, confirmed that the alternative splicing is attributable to the alleles of this variant. The predominateRPGRIP1L isoform expressed in adult brains does not contain exon 20; thus, a shift to include this exon may impact brain function.Mol Neuropsychiatry 2019;5(suppl 1):97 –105 (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - September 25, 2019 Category: Neuroscience Source Type: research
Importance of expanded carrier screening in the Ashkenazi Jewish population
Compared to the general population, patients of Ashkenazi Jewish descent have an increased risk of being genetic carriers for certain diseases, with an overall carrier rate ranging from 1 in 4 to 1 in 51. Therefore, the American College of Obstetricians and Gynecologists (ACOG) strongly recommends this population be offered carrier screening for four conditions: Tay Sachs, Cystic Fibrosis, Familial Dysautonomia, and Canavan Disease2. Some experts have advocated for a more comprehensive screening panel, and subsequently, ACOG recognized that screening for the following Jewish Genetic Diseases can be offered to patients: Blo...
Source: Fertility and Sterility - August 31, 2019 Category: Reproduction Medicine Authors: Shelley N. Dolitsky, Shama Khan, Elena Ashkinadze Tags: Poster session Source Type: research
Small GTPases in hedgehog signalling: emerging insights into the disease mechanisms of Rab23-mediated and Arl13b-mediated ciliopathies.
Abstract
Small GTPases are known to have pivotal roles in intracellular trafficking, and several members of the small GTPases superfamily such as Rab10 [1,2•], Rab11 [3-5], Rab34 [6•,7], Rab8 [3,8], Rab23 [9-12], RSG1 [13-15], Arl13b [16-22], and Arl6 [22,23] were recently reported to mediate primary cilia function and/or Hh signalling. Although these functions are implicated in diseases such as ciliopathies, the molecular basis underlying how these small GTPases mediate primary cilia-dependent Hh signalling and pathogenesis of ciliopathies warrants further investigations. Notably, Rab23 and Arl13b hav...
Source: Current Opinion in Genetics and Development - August 25, 2019 Category: Genetics & Stem Cells Authors: Hor CH, Goh EL Tags: Curr Opin Genet Dev Source Type: research
A CEP104-CSPP1 Complex Is Required for Formation of Primary Cilia Competent in Hedgehog Signaling
Publication date: 13 August 2019Source: Cell Reports, Volume 28, Issue 7Author(s): Kari-Anne M. Frikstad, Elisa Molinari, Marianne Thoresen, Simon A. Ramsbottom, Frances Hughes, Stef J.F. Letteboer, Sania Gilani, Kay O. Schink, Trond Stokke, Stefan Geimer, Lotte B. Pedersen, Rachel H. Giles, Anna Akhmanova, Ronald Roepman, John A. Sayer, Sebastian PatzkeSummaryCEP104 is an evolutionarily conserved centrosomal and ciliary tip protein. CEP104 loss-of-function mutations are reported in patients with Joubert syndrome, but their function in the etiology of ciliopathies is poorly understood. Here, we show that cep104 silencing i...
Source: Cell Reports - August 14, 2019 Category: Cytology Source Type: research
