PubMed Latest Articles

This section contains a feed from PubMed with recent papers on 'ciliopathy', with hyperlinked titles.
When you are on the PubMed site, you can search using any cilia and ciliopathy-related keywords or terms.

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06 March 2021

  • Primary Ciliary Dyskinesia Diagnostic Challenges: Understanding the Clinical Phenotype of the Puerto Rican RSPH4A Founder Mutation
    Primary ciliary dyskinesia (PCD) is a rare, heterogeneous ciliopathy resulting in chronic oto-sino-pulmonary disease, bronchiectasis, newborn respiratory distress, and laterality defects. PCD diagnosis can be achieved by following diagnostic algorithms that include electron microscopy, genetics, and ancillary testing. Genetic mutations in more than 45 genes, including RSPH4A, can lead to PCD. RSPH4A mutations located on chromosome six, affect radial spokes and results in central complex...
  • Prevalent ALMS1 Pathogenic Variants in Spanish Alström Patients
    Alström syndrome (ALMS) is an ultrarare disease with an estimated prevalence lower than 1 in 1,000,000. It is associated with disease-causing mutations in the Alström syndrome 1 (ALMS1) gene, which codifies for a structural protein of the basal body and centrosomes. The symptomatology involves nystagmus, type 2 diabetes mellitus (T2D), obesity, dilated cardiomyopathy (DCM), neurodegenerative disorders and multiorgan fibrosis. We refined the clinical and genetic diagnosis data of 12 patients from...
  • Ectopic expression of BBS1 rescues male infertility, but not retinal degeneration, in a BBS1 mouse model
    Bardet-Biedl syndrome (BBS) is a rare ciliopathy for which there are no current effective treatments. BBS is a genetically heterogeneous disease, though the M390R mutation in BBS1 is involved in ~25% of all genetic diagnoses of BBS. The principle features of BBS include retinal degeneration, obesity, male infertility, polydactyly, intellectual disability, and renal abnormalities. Patients with mutations in BBS genes often present with night blindness within the first decade of life, which...
  • Centrosome-phagy: implications for human diseases
    Autophagy is a prominent mechanism to preserve homeostasis and the response to intracellular or extracellular stress. Autophagic degradation can be selectively targeted to dysfunctional subcellular compartments. Centrosome homeostasis is pivotal for healthy proliferating cells, but centrosome aberration is a hallmark of diverse human disorders. Recently, a process called centrosome-phagy has been identified. The process involves a panel of centrosomal proteins and centrosome-related pathways...
  • nNOS regulates ciliated cell polarity, ciliary beat frequency, and directional flow in mouse trachea
    Clearance of the airway is dependent on directional mucus flow across the mucociliary epithelium, and deficient flow is implicated in a range of human disorders. Efficient flow relies on proper polarization of the multiciliated cells and sufficient ciliary beat frequency. We show that NO, produced by nNOS in the multiciliated cells of the mouse trachea, controls both the planar polarity and the ciliary beat frequency and is thereby necessary for the generation of the robust flow. The effect of...
  • Ciliary neuropeptidergic signaling dynamically regulates excitatory synapses in postnatal neocortical pyramidal neurons
    Primary cilia are compartmentalized sensory organelles present on the majority of neurons in the mammalian brain throughout adulthood. Recent evidence suggests that cilia regulate multiple aspects of neuronal development, including the maintenance of neuronal connectivity. However, whether ciliary signals can dynamically modulate postnatal circuit excitability is unknown. Here we show that acute cell-autonomous knockdown of ciliary signaling rapidly strengthens glutamatergic inputs onto cultured...
  • CiliOPD: a ciliopathy-associated COPD endotype
    The pathophysiology of chronic obstructive pulmonary disease (COPD) relies on airway remodelling and inflammation. Alterations of mucociliary clearance are a major hallmark of COPD caused by structural and functional cilia abnormalities. Using transcriptomic databases of whole lung tissues and isolated small airway epithelial cells (SAEC), we comparatively analysed cilia-associated and ciliopathy-associated gene signatures from a set of 495 genes in 7 datasets including 538 non-COPD and 508 COPD...
  • Mendelian pathway analysis of laboratory traits reveals distinct roles for ciliary subcompartments in common disease pathogenesis
    Rare monogenic disorders of the primary cilium, termed ciliopathies, are characterized by extreme presentations of otherwise common diseases, such as diabetes, hepatic fibrosis, and kidney failure. However, despite a recent revolution in our understanding of the cilium's role in rare disease pathogenesis, the organelle's contribution to common disease remains largely unknown. Hypothesizing that common genetic variants within Mendelian ciliopathy genes might contribute to common complex diseases...
  • IFT46 Expression in the Nasal Mucosa of Primary Ciliary Dyskinesia Patients: Preliminary Study
    BACKGROUND: Primary ciliary dyskinesia (PCD) is characterised by an imbalance in mucociliary clearance leading to chronic respiratory infections. Cilia length is considered to be a contributing factor in cilia movement. Recently, IFT46 protein has been related to cilia length. Therefore, this work aims to study IFT46 expression in a PCD patients cohort and analyse its relationship with cilia length and function, as it was not previously described.
  • Knockout of the CEP290 gene in human induced pluripotent stem cells
    CEP290 is a principal component of the primary cilium and is important for the proper function of ciliated cells. CEP290 mutations have been linked to numerous ciliopathies, with a wide range of phenotypic severities, but with poor genotype:phenotype correlation. Here we have used CRISPR/Cas9 technology to target the CEP290 gene and generate a line of induced pluripotent stem cells that lack detectable CEP290 expression, but retain a normal karyotype and differentiation potential. This line of...
  • Rpgrip1l controls ciliary gating by ensuring the proper amount of Cep290 at the vertebrate transition zone
    A range of severe human diseases called ciliopathies are caused by the dysfunction of primary cilia. Primary cilia are cytoplasmic protrusions consisting of the basal body (BB), the axoneme and the transition zone (TZ). The BB is a modified mother centriole from which the axoneme, the microtubule-based ciliary scaffold, is formed. At the proximal end of the axoneme, the TZ functions as the ciliary gate governing ciliary protein entry and exit. Since ciliopathies often develop due to mutations in...
  • Sensenbrenner syndrome: a further challenge in evaluating sagittal synostosis and a need for a multidisciplinary approach
    BACKGROUND: Sensenbrenner syndrome, also known as cranioectodermal dysplasia (CED), is a genetically heterogeneous ciliopathy, characterized by dysmorphic features including dolichocephaly (with inconstant sagittal craniosynostosis), chronic kidney disease (CKD), hepatic fibrosis, retinitis pigmentosa, and brain abnormalities, with a partial clinical overlap with other ciliopathies.
  • The Multifaceted Roles of Primary Cilia in the Development of the Cerebral Cortex
    The primary cilium, a microtubule based organelle protruding from the cell surface and acting as an antenna in multiple signaling pathways, takes center stage in the formation of the cerebral cortex, the part of the brain that performs highly complex neural tasks and confers humans with their unique cognitive capabilities. These activities require dozens of different types of neurons that are interconnected in complex ways. Due to this complexity, corticogenesis has been regarded as one of the...
  • Retinal dystrophy as part of TTC21B-associated ciliopathy
    Background: TCC21B is a ciliary protein. The most common phenotypic features associated with TCC21B biallelic mutations are nephronophthisis and skeletal abnormalities. To date, retinal dystrophy has been reported in only one patient. Materials and Methods: Clinical evaluation included best-corrected visual acuity, cycloplegic refraction, fundus examination, fundus photography, retinal imaging by optical coherence tomography, full-field electroretinography, multifocal electroretinography, and...
  • ALMS1 Regulates TGF-β Signaling and Morphology of Primary Cilia
    In this study, we aimed to evaluate the role of ALMS1 in the morphology of primary cilia and regulation of cellular signaling using a knockdown model of the hTERT-RPE1 cell line. ALMS1 depletion resulted in the formation of longer cilia, which often displayed altered morphology as evidenced by extensive twisting and bending of the axoneme. Transforming growth factor beta/bone morphogenetic protein (TGF-β/BMP) signaling, which is regulated by primary cilia, was similarly affected by ALMS1...
  • Leber Congenital Amaurosis Due to CEP290 Mutations - Severe Vision Impairment with a High Unmet Medical Need: A Review
    CONCLUSIONS: Interventions that can preserve or improve vision in patients with LCA10 have considerable potential to improve patient quality of life and reduce burden of disease.
  • Successful Reuse of a Transplanted Kidney 9 Years after Transplantation
    No abstract
  • Early clinical management of autosomal recessive polycystic kidney disease
    Autosomal recessive polycystic kidney disease (ARPKD) is a rare but highly relevant disorder in pediatric nephrology. This genetic disease is mainly caused by variants in the PKHD1 gene and is characterized by fibrocystic hepatorenal phenotypes with major clinical variability. ARPKD frequently presents perinatally, and the management of perinatal and early disease symptoms may be challenging. This review discusses aspects of early manifestations in ARPKD and its clincial management with a...
  • Ciliopathic micrognathia is caused by aberrant skeletal differentiation and remodeling
    Ciliopathies represent a growing class of diseases caused by defects in microtubule-based organelles called primary cilia. Approximately 30% of ciliopathies are characterized by craniofacial phenotypes such as craniosynostosis, cleft lip/palate and micrognathia. Patients with ciliopathic micrognathia experience a particular set of difficulties, including impaired feeding and breathing, and have extremely limited treatment options. To understand the cellular and molecular basis for ciliopathic...
  • Identification of additional outer segment targeting signals in zebrafish rod opsin
    In vertebrate photoreceptors, opsins are highly concentrated in a morphologically distinct ciliary compartment known as the outer segment (OS). Opsin is synthesized in the cell body and transported to the OS at a remarkable rate of 100-1000 molecules per second. Opsin transport defects contribute to photoreceptor loss and blindness in human ciliopathies. Previous studies revealed that the opsin C-terminal tail, of 44 amino acids, is sufficient to mediate OS targeting in Xenopus photoreceptors....
  • Xenopus to the rescue: A model to validate and characterize candidate ciliopathy genes
    Cilia are present on most vertebrate cells and play a central role in development, growth, and homeostasis. Thus, cilia dysfunction can manifest into an array of diseases, collectively termed ciliopathies, affecting millions of lives worldwide. Yet, our understanding of the gene regulatory networks that control cilia assembly and functions remain incomplete. With the advances in next-generation sequencing technologies, we can now rapidly predict pathogenic variants from hundreds of ciliopathy...