PubMed Latest Articles

23 May 2022

• Adult Presentation of Joubert Syndrome Presenting With Dysphagia: A Case Report
  Joubert syndrome (JS) is a rare autosomal recessive disease affecting the cilium, an intracellular organelle. It has a wide spectrum of presentations with the involvement of multiple genes. JS has multiple subtypes that are either pure JS or JS with other organ involvement such as the kidneys, liver, and others. However, all subtypes share the involvement of the cerebellar peduncles and the brainstem, which presents as "a molar tooth sign" on magnetic resonance imaging, hypotonia, and...
• Fetal phenotypes of Mendelian disorders: A descriptive study from India
  CONCLUSION: This cohort demonstrates how deep fetal phenotypes of some Mendelian disorders can show novel/unusual findings which have important implications for prenatal diagnosis of these conditions. This article is protected by copyright. All rights reserved.
• Asymptomatic Pyuria as a Prognostic Biomarker in Autosomal Dominant Polycystic Kidney Disease
  CONCLUSIONS: AP is associated with kidney failure and faster kidney function decline irrespective of the ADPKD gene, cystic burden, and cystic growth. These results support AP as an enriching prognostic biomarker for the rate of disease progression.
• An eye on the future for defeating hydrocephalus, ciliary dyskinesia-related hydrocephalus: review article
  Congenital hydrocephalus affects approximately one in 1000 newborn children and is fatal in approximately 50% of untreated cases. The currently known management protocols usually necessitate multiple interventions and long-term use of healthcare resources due to a relatively high incidence of complications, and many of them mostly provide a treatment of the effect rather than the cause of cerebrospinal fluid flow reduction or outflow obstruction. Future studies discussing etiology specific...
• Ciliary central apparatus structure reveals mechanisms of microtubule patterning
  A pair of extensively modified microtubules form the central apparatus (CA) of the axoneme of most motile cilia, where they regulate ciliary motility. The external surfaces of both CA microtubules are patterned asymmetrically with large protein complexes that repeat every 16 or 32 nm. The composition of these projections and the mechanisms that establish asymmetry and longitudinal periodicity are unknown. Here, by determining cryo-EM structures of the CA microtubules, we identify 48 different...
• Roles of the actin cytoskeleton in ciliogenesis
  Primary cilia play a key role in the ability of cells to respond to extracellular stimuli, such as signaling molecules and environmental cues. These sensory organelles are crucial to the development of many organ systems, and defects in primary ciliogenesis lead to multisystemic genetic disorders, known as ciliopathies. Here, we review recent advances in the understanding of several key aspects of the regulation of ciliogenesis. Primary ciliogenesis is thought to take different pathways...
• Long-Term Outcomes of Kidney Transplant Recipients With Juvenile Nephronophthisis
  CONCLUSIONS: Posttransplant prognosis was good among kidney transplant recipients with juvenile nephronophthisis.
• Two Cases With Neonatal Cholestasis and Renal Disorders Due to DCDC2 Mutation
  Ciliopathies are a heterogeneous group of diseases that are observed after deterioration of the ciliary structures on the cell surface that facilitate communication with the environment. Both liver and kidney involvement are frequently observed in this disease. Recently, a doublecortin domain containing protein 2 (DCDC2) mutation in a ciliopathy disease group was identified. Here, we present 2 patients with this mutation and with neonatal cholestasis and renal involvement.
• Genetic Kidney Diseases (GKDs) Modeling Using Genome Editing Technologies
  Genetic kidney diseases (GKDs) are a group of rare diseases, affecting approximately about 60 to 80 per 100,000 individuals, for which there is currently no treatment that can cure them (in many cases). GKDs usually leads to early-onset chronic kidney disease, which results in patients having to undergo dialysis or kidney transplant. Here, we briefly describe genetic causes and phenotypic effects of six GKDs representative of different ranges of prevalence and renal involvement (ciliopathy,...
• Clinical and genetic spectrums of 413 North African families with inherited retinal dystrophies and optic neuropathies
  BACKGROUND: Inherited retinal dystrophies (IRD) and optic neuropathies (ION) are the two major causes world-wide of early visual impairment, frequently leading to legal blindness. These two groups of pathologies are highly heterogeneous and require combined clinical and molecular diagnoses to be securely identified. Exact epidemiological studies are lacking in North Africa, and genetic studies of IRD and ION individuals are often limited to case reports or to some families that migrated to the...
• Control of meiotic chromosomal bouquet and germ cell morphogenesis by the zygotene cilium
  A hallmark of meiosis is chromosomal pairing, which requires telomere tethering and rotation on the nuclear envelope via microtubules, driving chromosome homology searches. Telomere pulling toward the centrosome forms the "zygotene chromosomal bouquet". Here, we identified the "zygotene cilium" in oocytes. This cilium provides a cable system for the bouquet machinery, extending throughout the germline cyst. Using zebrafish mutants and live manipulations, we demonstrate that the cilium anchors...
• Clinical phenotypes of primary ciliary dyskinesia
  Primary ciliary dyskinesia (PCD) is a hereditary disease characterized by airway mucociliary clearance dysfunction. The estimated prevalence of PCD is 1꞉10 000 to 1꞉20 000. The main respiratory manifestations in children are cough, expectoration, chronic rhinitis, sinusitis, and chronic otitis media, while the most common symptoms in adults are chronic sinusitis, bronchiectasis, and infertility. About 50% of patients with certain PCD-related gene variants are combined with situs inversus, and...
• Cilia-localized GID/CTLH ubiquitin ligase complex regulates protein homeostasis of sonic hedgehog signaling components
  Cilia are evolutionarily conserved organelles that orchestrate a variety of signal transduction pathways, such as sonic hedgehog (SHH) signaling, during embryonic development. Our recent studies have shown that loss of GID ubiquitin ligase function results in aberrant AMP-activated protein kinase (AMPK) activation and elongated primary cilia, which suggests a functional connection to cilia. Here, we reveal that the GID complex is an integral part of the cilium required for primary...
• Multidisciplinary neurocutaneous syndrome clinics: a systematic review and institutional experience
  CONCLUSIONS: To the best of the authors' knowledge, this is the first detailed description of a comprehensive pediatric neurocutaneous clinic in the US that serves patients with multiple syndromes. There is currently heterogeneity between described multidisciplinary clinic structures and practices. More detailed accounts of clinic compositions and practices along with patient data and outcomes are needed in order to establish the most comprehensive and efficient multidisciplinary approach for...
• Reducing exacerbations in children and adults with primary ciliary dyskinesia using erdosteine and/or azithromycin therapy (REPEAT trial): study protocol for a multicentre, double-blind, double-dummy, 2×2 partial factorial, randomised controlled trial
  INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare, progressive, inherited ciliopathic disorder, which is incurable and frequently complicated by the development of bronchiectasis. There are few randomised controlled trials (RCTs) involving children and adults with PCD and thus evidence of efficacy for interventions are usually extrapolated from people with cystic fibrosis. Our planned RCT seeks to address some of these unmet needs by employing a currently prescribed (but unapproved for...
• Nephronophthisis: a pediatric case report
  Nephronophthisis is an autosomal recessive cystic kidney disease caused by mutations in genes that encode proteins involved in the primary cilia function, resulting in kidney disease and extrarenal manifestations such as retinal degeneration and liver fibrosis. According to the age of development of end-stage chronic kidney disease, three clinical forms of presentation are described: infantile, juvenile and adolescent. Diagnosis is made by a positive genetic test, or a kidney biopsy...
• Combined therapy guided by multimodal imaging of fifteen retinal capillary hemangioblastomas in a monocular Von Hippel- Lindau syndrome case report
  CONCLUSION: For multiple retinal capillary hemangioblastomas in monocular patients, precise combined therapy guided by multimodal imaging has a profound impact on the management of new and recurrent RCHs.
• Mechanism of tethered agonist-mediated signaling by polycystin-1
  SignificanceMutations of polycystin-1 (PC1) are the major cause (85% of cases) of autosomal dominant polycystic kidney disease (ADPKD), which is the fourth leading cause of kidney failure. PC1 is thought to function as an atypical G protein-coupled receptor, yet the mechanism by which PC1 regulates G-protein signaling remains poorly understood. A significant portion of ADPKD mutations of PC1 encode a protein with defects in maturation or reduced function that may be amenable to functional...
• Characterization of two novel knock-in mouse models of syndromic retinal ciliopathy carrying hypomorphic Sdccag8 mutations
  Mutations in serologically defined colon cancer autoantigen protein 8 ( SDCCAG8) were first identified in retinal ciliopathy families a decade ago with unknown function. To investigate the pathogenesis of SDCCAG8-associated retinal ciliopathies in vivo, we employed CRISPR/Cas9-mediated homology-directed recombination (HDR) to generate two knock-in mouse models, Sdccag8 ^(Y236X/Y236X) and Sdccag8 ^(E451GfsX467/E451GfsX467) , which carry truncating mutations of the mouse Sdccag8, corresponding to...
• Polycystic Kidney/Liver Disease
  Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder that leads to chronic kidney disease and end-stage kidney disease (ESKD). Polycystic liver disease (PCLD) is the most common extrarenal manifestation of ADPKD. Though isolated PCLD and PCLD due to ADPKD are genetically distinct, they follow a similar clinical course of hepatomegaly from multiple cysts with preserved liver function. Tolvaptan use in ADPKD can slow down the deterioration of renal function and growth of...
• Delineating and sparing functional nephrons for radiotherapy in the case of lymphoma with polycystic kidney disease
  CONCLUSIONS: Delineation of functional nephrons was feasible while utilizing the staging FDG-PETCT scan for radiotherapy contouring in our patient, which aided to achieve the optimal dose-volume constraints. Further studies are warranted to analyze and quantify the benefit of this easily accessible method in the future.