Disease-Associated Mutations in CEP120 Destabilize the Protein and Impair Ciliogenesis
Publication date: 29 May 2018 Source:Cell Reports, Volume 23, Issue 9 Author(s): Nimesh Joseph, Caezar Al-Jassar, Christopher M. Johnson, Antonina Andreeva, Deepak D. Barnabas, Stefan M.V. Freund, Fanni Gergely, Mark van Breugel Ciliopathies are a group of genetic disorders caused by a failure to form functional cilia. Due to a lack of structural information, it is currently poorly understood how ciliopathic mutations affect protein functionality to give rise to the underlying disease. Using X-ray crystallography, we show that the ciliopathy-associated centriolar protein CEP120 contains three C2 domains. The poi...
Source: Cell Reports - May 30, 2018 Category: Cytology Source Type: research
Sleep in Children with Congenital Malformations of the Central Nervous System
AbstractPurpose of ReviewCongenital malformations of the central nervous system may be seen in isolation or in association with syndromes that have multiorgan involvement. Among the potential health challenges these children may face, sleep concerns are frequent and may include chronic insomnia, sleep-related breathing disorders, and circadian rhythm disorders.Recent FindingsIn this review, we describe recent research into sleep disorders affecting children with congenital malformations of the CNS including visual impairment, septo-optic dysplasia, agenesis of the corpus callosum, Aicardi syndrome, Chiari malformation, spi...
Source: Current Neurology and Neuroscience Reports - May 23, 2018 Category: Neuroscience Source Type: research
A novel Cep120-dependent mechanism inhibits centriole maturation in quiescent cells
The two centrioles of the centrosome in quiescent cells are inherently asymmetric structures that differ in age, morphology and function. How these asymmetric properties are established and maintained during quiescence remains unknown. Here we show that a daughter centriole-associated ciliopathy protein, Cep120, plays a critical inhibitory role at daughter centrioles. Depletion of Cep120 in quiescent mouse and human cells causes accumulation of pericentriolar material (PCM) components including Pericentrin, Cdk5Rap2, Ninein and Cep170. The elevated PCM levels result in increased microtubule-nucleation activity at the centr...
Source: eLife - May 9, 2018 Category: Biomedical Science Tags: Cell Biology Source Type: research
Tyrosine hydroxylase down-regulation after loss of Abelson helper integration site 1 (AHI1) promotes depression via the circadian clock pathway in mice [Cell Biology]
Abelson helper integration site 1 (AHI1) is associated with several neuropsychiatric and brain developmental disorders, such as schizophrenia, depression, autism, and Joubert syndrome. Ahi1 deficiency in mice leads to behaviors typical of depression. However, the mechanisms by which AHI1 regulates behavior remain to be elucidated. Here, we found that down-regulation of expression of the rate-limiting enzyme in dopamine biosynthesis, tyrosine hydroxylase (TH), in the midbrains of Ahi1-knockout (KO) mice is responsible for Ahi1-deficiency–mediated depressive symptoms. We also found that Rev-Erbα, a TH transcriptional repr...
Source: Journal of Biological Chemistry - April 6, 2018 Category: Chemistry Authors: Dongkai Guo, Shun Zhang, Hongyang Sun, Xingyun Xu, Zongbing Hao, Chenchen Mu, Xingshun Xu, Guanghui Wang, Haigang Ren Tags: Molecular Bases of Disease Source Type: research
F200. elucidating the role of cilia in neuropsychiatric diseases through interactome analysis
DiscussionCiliary genes like DRD1 and DRD2 are implicated in neurotransmission and associated with schizophrenia. DRD1 has 4 novel interactors and DRD2 has 12 novel interactors that may have significant role in the pathology of mental disorders. Neuronal pathways associated with cilia interactome with high statistical significance such as dopamine signaling, eNOS signaling, synaptic long-term potentiation pathways are known to be associated schizophrenia. Wnt signaling and PCP signaling are also known to be associated with cilia mediated neurodevelopmental signaling, defects in these pathways contributing to schizophrenia....
Source: Schizophrenia Bulletin - April 1, 2018 Category: Psychiatry Source Type: research
Novel mutations in the ciliopathy-associated gene CPLANE1 (C5orf42) cause OFD syndrome type VI rather than Joubert syndrome.
, Kariminejad A
Abstract
Mutations in CPLANE1 (previously known as C5orf42) cause Oral-Facial-Digital Syndrome type VI (OFD6) as well as milder Joubert syndrome (JS) phenotypes. Seven new cases from five unrelated families diagnosed with pure OFD6 were systematically examined. Based on the clinical manifestations of these patients and those described in the literature, we revised the diagnostic features of OFD6 and include the seven most common characteristics: 1) molar tooth sign, 2) tongue hamartoma and/or lobulated tongue, 3) additional frenula, 4) mesoaxial polydactyly of hands, 5) preaxial polydactyly ...
Source: European Journal of Medical Genetics - March 29, 2018 Category: Genetics & Stem Cells Authors: Bonnard C, Shboul M, Tonekaboni SH, Ng AYJ, Tohari S, Ghosh K, Lai A, Lim JY, Tan EC, Devisme L, Stichelbout M, Alkindi A, Banu N, Yüksel Z, Ghoumid J, Elkhartoufi N, Boutaud L, Micalizzi A, Brett MS, Venkatesh B, Valente EM, Attié-Bitach T, Reversade B Tags: Eur J Med Genet Source Type: research
The fourth ventricle index - a sonographic marker for severe fetal vermian dysgenesis / agenesis.
CONCLUSIONS: The 4VI is sonographic marker for severe fetal vermian dysgenesis / agenesis in the absence of an open 4v. It may be easily incorporated into the routine brain scan and a 4VI <1 indicate the need of dedicated fetal neuroimaging studies for appropriate diagnosis and prenatal counseling.
PMID: 29484745 [PubMed - as supplied by publisher] (Source: The Ultrasound Review of Obstetrics and Gynecology)
Source: The Ultrasound Review of Obstetrics and Gynecology - February 26, 2018 Category: Radiology Authors: Haratz KK, Shulevitz SL, Leibovitz Z, Lev D, Josef S, Tomarkin M, Malinger G, Lerman-Sagie T, Gindes L Tags: Ultrasound Obstet Gynecol Source Type: research
The fourth ventricle index – a sonographic marker for severe fetal vermian dysgenesis / agenesis
ConclusionsThe 4VI is sonographic marker for severe fetal vermian dysgenesis / agenesis in the absence of an open 4v. It may be easily incorporated into the routine brain scan and a 4VI <1 indicate the need of dedicated fetal neuroimaging studies for appropriate diagnosis and prenatal counseling. (Source: Ultrasound in Obstetrics and Gynecology)
Source: Ultrasound in Obstetrics and Gynecology - February 26, 2018 Category: Radiology Authors: Karina Krajden Haratz, Sharon Leshem Shulevitz, Zvi Leibovitz, Dorit Lev, Shalev Josef, Mordechai Tomarkin, Gustavo Malinger, Tally Lerman ‐Sagie, Liat Gindes Tags: Original Paper Source Type: research
Characteristics of Liver Disease in 100 Individuals With Joubert Syndrome Prospectively Evaluated at a Single Center
Conclusions:In JS, probable portal hypertension is associated with abnormal hepatic enzymes, as well as presence of kidney disease, coloboma, and/or mutation in TMEM67. These findings may allow early identification of JS patients who have or are more likely to develop liver disease.
Background and Aims:
Joubert Syndrome (JS) is a rare, inherited, ciliopathy defined by cerebellar and brainstem malformations and is variably associated with liver, kidney, and ocular dysfunction. This study characterizes the hepatic findings in JS and identifies factors associated with probable portal hypertension.
Methods:
Hundred indi...
Source: Journal of Pediatric Gastroenterology and Nutrition - February 24, 2018 Category: Gastroenterology Tags: Original Articles: Hepatology Source Type: research
Cep120 promotes microtubule formation through a unique tubulin binding C2 domain
Publication date: Available online 1 February 2018 Source:Journal of Structural Biology Author(s): Ashwani Sharma, Samuel F. Gerard, Natacha Olieric, Michel O. Steinmetz Centrioles are microtubule-based structures that play essential roles in cell division and cilia biogenesis. Cep120 is an important protein for correct centriole formation and mutations in the Cep120 gene cause severe human diseases like Joubert syndrome and complex ciliopathies. Here, we show that Cep120 contains three consecutive C2 domains that are followed by a coiled-coil dimerization domain. Surprisingly, unlike the classical C2 domains, all th...
Source: Journal of Structural Biology - February 2, 2018 Category: Biology Source Type: research
Production and characterization of human induced pluripotent stem cells (iPSCs) from Joubert Syndrome: CSSi001-A (2850)
Publication date: Available online 9 January 2018 Source:Stem Cell Research Author(s): Jessica Rosati, Filomena Altieri, Silvia Tardivo, Elisa Maria Turco, Marina Goldoni, Iolanda Spasari, Daniela Ferrari, Laura Bernardini, Giuseppe Lamorte, Enza Maria Valente, Angelo Luigi Vescovi Joubert Syndrome (JS) is a rare autosomal recessive or X-linked condition characterized by a peculiar cerebellar malformation, known as the molar tooth sign (MTS), associated with other neurological phenotypes and multiorgan involvement. JS is a ciliopathy, a spectrum of disorders whose causative genes encode proteins involved in th...
Source: Stem Cell Research - January 11, 2018 Category: Stem Cells Source Type: research
The guanine nucleotide exchange factor Arf-like protein 13b is essential for assembly of the mouse photoreceptor transition zone and outer segment [Neurobiology]
Arf-like protein 13b (ARL13b) is a small GTPase that functions as a guanosine nucleotide exchange factor (GEF) for ARL3-GDP. ARL13b is located exclusively in photoreceptor outer segments (OS) presumably anchored to discs by palmitoylation, whereas ARL3 is an inner segment cytoplasmic protein. Hypomorphic mutations affecting the ARL13b G-domain inactivate GEF activity and lead to Joubert syndrome (JS) in humans. However, the molecular mechanisms in ARL13b mutation–induced Joubert syndrome, particularly the function of primary cilia, are still incompletely understood. Because Arl13b germline knockouts in mouse are lethal, ...
Source: Journal of Biological Chemistry - December 29, 2017 Category: Chemistry Authors: Christin Hanke-Gogokhia, Zhijian Wu, Ali Sharif, Hussein Yazigi, Jeanne M. Frederick, Wolfgang Baehr Tags: Molecular Bases of Disease Source Type: research
Anterior Mesencephalic Cap Dysplasia: Novel Brain Stem Malformative Features Associated with Joubert Syndrome [PEDIATRICS]
SUMMARY:
In Joubert syndrome, the "molar tooth" sign can be associated with several additional supra- and infratentorial malformations. Here we report on 3 subjects (2 siblings, 8–14 years of age) with Joubert syndrome, showing an abnormal thick bulging of the anterior profile of the mesencephalon causing a complete obliteration of the interpeduncular fossa. DTI revealed that the abnormal tissue consisted of an ectopic white matter tract with a laterolateral transverse orientation. Tractographic reconstructions support the hypothesis of impaired axonal guidance mechanisms responsible for the malformation. The 2 sibli...
Source: American Journal of Neuroradiology - December 15, 2017 Category: Radiology Authors: Arrigoni, F., Romaniello, R., Peruzzo, D., De Luca, A., Parazzini, C., Valente, E. M., Borgatti, R., Triulzi, F. Tags: PEDIATRICS Source Type: research
Arima syndrome caused by CEP290 specific variant and accompanied with pathological cilium; clinical comparison with Joubert syndrome and its related diseases
Arima syndrome (AS) is a rare disease and its clinical features mimic those of Joubert syndrome or Joubert syndrome-related diseases (JSRD). Recently, we clarified the AS diagnostic criteria and its severe phenotype. However, genetic evidence of AS remains unknown. We explored causative genes of AS and compared the clinical and genetic features of AS with the other JSRD. (Source: Brain and Development)
Source: Brain and Development - December 4, 2017 Category: Neurology Authors: Masayuki Itoh, Shuhei Ide, Yuji Iwasaki, Takashi Saito, Keishi Narita, Hongmei Dai, Shinji Yamakura, Takeki Furue, Hirotsugu Kitayama, Keiko Maeda, Eihiko Takahashi, Kiyoshi Matsui, Yu-ichi Goto, Sen Takeda, Masataka Arima Tags: Original article Source Type: research
Prenatal diagnosis of Joubert syndrome: A case report and literature review
Conclusions:Currently, a diagnosis of JS is commonly made after birth. Fewer cases of prenatal diagnosis by ultrasonography have been made, and they are more liable to be misdirected because of some nonspecial features that also manifest in Dandy-Walker malformation, cranio-cerebello-cardiac syndrome, and so on.
Introduction:
Joubert syndrome (JS) is a rare autosomal recessive inherited disease belonging to ciliopathy with the causative mutation of genes. Except for X-linked inheritance, the high recurrence rate of a family is about 25%. After birth, it may cause a series of neurological symptoms, even with retina, kid...
Source: Medicine - December 1, 2017 Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
