PubMed Latest Articles

02 December 2021

• Prenatal exome sequencing and chromosomal microarray analysis in fetal structural anomalies in a highly consanguineous population reveals a propensity of ciliopathy genes causing multisystem phenotypes
  Fetal abnormalities are detected in 3% of all pregnancies and are responsible for approximately 20% of all perinatal deaths. Chromosomal microarray analysis (CMA) and exome sequencing (ES) are widely used in prenatal settings for molecular genetic diagnostics with variable diagnostic yields. In this study, we aimed to determine the diagnostic yield of trio-ES in detecting the cause of fetal abnormalities within a highly consanguineous population. In families with a history of congenital...
• Evolutionarily conserved genetic interactions between nphp-4 and bbs-5 mutations exacerbate ciliopathy phenotypes
  Primary cilia are sensory and signaling hubs with a protein composition that is distinct from the rest of the cell due to the barrier function of the transition zone (TZ) at the base of the cilium. Protein transport across the TZ is mediated in part by the BBSome, and mutations disrupting TZ and BBSome proteins cause human ciliopathy syndromes. Ciliopathies have phenotypic variability even among patients with identical genetic variants, suggesting a role for modifier loci. To identify potential...
• Cilia locally synthesize proteins to sustain their ultrastructure and functions
  Cilia are microtubule-based hair-like organelles propelling locomotion and extracellular liquid flow or sensing environmental stimuli. As cilia are diffusion barrier-gated subcellular compartments, their protein components are thought to come from the cell body through intraflagellar transport or diffusion. Here we show that cilia locally synthesize proteins to maintain their structure and functions. Multicilia of mouse ependymal cells are abundant in ribosomal proteins, translation initiation...
• Genome-wide screening in human kidney organoids identifies developmental and disease-related aspects of nephrogenesis
  Human organoids allow the study of proliferation, lineage specification, and 3D tissue development. Here we present a genome-wide CRISPR screen in induced pluripotent stem cell (iPSC)-derived kidney organoids. The combination of inducible genome editing, longitudinal sampling, and endpoint sorting of tubular and stromal cells generated a complex, high-quality dataset uncovering a broad spectrum of insightful biology from early development to "adult" epithelial morphogenesis. Our functional...
• Get Your Molar Tooth Right: Joubert Syndrome Misdiagnosis Unmasked by Whole-Exome Sequencing
  Joubert syndrome (JS) is a recessively inherited ciliopathy, characterized by a specific cerebellar and brainstem malformation recognizable on brain imaging as the "molar tooth sign" (MTS). Clinical signs include hypotonia, developmental delay, breathing abnormalities, and ocular motor apraxia. Older patients develop ataxia, intellectual impairment, and variable organ involvement. JS is genetically heterogeneous, with over 40 ciliary genes overall accounting for 65-75% cases. Thus, in recent...
• Genetic testing and prenatal diagnosis for a Chinese pedigree affected with Meckel-Gruber syndrome
  CONCLUSION: The compound heterozygous variants of the CEP290 gene probably underlay the pathogenesis of Meckel-Gruber syndrome in the second fetus. Above finding has provided a basis for genetic counseling and prenatal diagnosis for the couple, and also enriched the mutational spectrum of the CEP290 gene.
• Insights into the Regulation of Ciliary Disassembly
  The primary cilium, an antenna-like structure that protrudes out from the cell surface, is present in most cell types. It is a microtubule-based organelle that serves as a mega-signaling center and is important for sensing biochemical and mechanical signals to carry out various cellular processes such as proliferation, migration, differentiation, and many others. At any given time, cilia length is determined by a dynamic balance of cilia assembly and disassembly processes. Abnormally short or...
• The Role of Centrosome Distal Appendage Proteins (DAPs) in Nephronophthisis and Ciliogenesis
  The primary cilium is found in most mammalian cells and plays a functional role in tissue homeostasis and organ development by modulating key signaling pathways. Ciliopathies are a group of genetically heterogeneous disorders resulting from defects in cilia development and function. Patients with ciliopathic disorders exhibit a range of phenotypes that include nephronophthisis (NPHP), a progressive tubulointerstitial kidney disease that commonly results in end-stage renal disease (ESRD). In...
• Expanding the Phenotype of the FAM149B1-Related Ciliopathy and Identification of Three Neurogenetic Disorders in a Single Family
  Biallelic truncating FAM149B1 variants result in cilia dysfunction and have been reported in four infants with Joubert syndrome and orofaciodigital syndrome type VI, respectively. We report here on three adult siblings, 18 to 40 years of age, homozygous for the known FAM149B1 c.354_357delinsCACTC (p.Gln118Hisfs*20) variant. Detailed clinical examinations were performed including ocular and gait analyses, skeletal- and neuroimaging. All three patients presented with neurological and oculomotor...
• Meckel Gruber and Joubert Syndrome Diagnosed Prenatally: Allelism between the Two Ciliopathies, Complexities of Mutation Types and Digenic Inheritance
  Background: Antenatally detected occipital encephalocele and polycystic kidneys are a common presentation of ciliopathies like Joubert syndrome and Meckel Gruber syndrome which have considerable genetic and phenotypic overlap. Case reports: We describe 3 cases of antenatally diagnosed occipital encephalocele and enlarged kidneys with fetal autopsy, histopathology & exome sequencing results. A novel nonsense variant in the CEP290 gene was reported in first case (Meckel syndrome). The second case...
• LUBAC regulates ciliogenesis by promoting CP110 removal from the mother centriole
  Primary cilia transduce diverse signals in embryonic development and adult tissues. Defective ciliogenesis results in a series of human disorders collectively known as ciliopathies. The CP110-CEP97 complex removal from the mother centriole is an early critical step for ciliogenesis, but the underlying mechanism for this step remains largely obscure. Here, we reveal that the linear ubiquitin chain assembly complex (LUBAC) plays an essential role in ciliogenesis by targeting the CP110-CEP97...
• Tubuloglomerular Disease With Cone-Shaped Epiphyses Associated With Hypomorphic Variant and a Novel p.Cys14Arg in the TTC21B Gene: A Case Report
  Monogenic nephrotic syndrome (NS) is associated with a resistance to initial glucocorticoid therapy and causative variants, which may be found in several genes influencing podocyte stability and kidney development. The TTC21B gene, which encodes the retrograde intraflagellar transport protein IFT139, is found mostly in association with ciliopathies in humans. The role of this protein in podocyte cytoskeleton stability was confirmed later and the mutated TTC21B also may be associated with...
• Tumor Syndromes: Neurosurgical Evaluation and Management
  There are multiple syndromes associated with tumors of the central nervous system (CNS). The most common CNS tumor syndrome is neurofibromatosis-1, with well-defined major and minor criteria needed for diagnosis. Other syndromes with variable degree of CNS and extra-CNS involvement that the neurosurgeon should be aware of include neurofibromatosis-2; Turcot syndrome; Cowden syndrome; Gorlin syndrome; Li-Fraumeni syndrome; ataxia-telangiectasia; multiple endocrine neoplasia type 1; von...
• Right Ventricular Blood Cyst in an Adult Autosomal Dominant Polycystic Kidney Disease Patient:<br /> An Unusual Association
  Blood cysts of the heart are unusual primary cardiac tumor-like masses, which are usually located on the cardiac valves. These are very rare in adults, especially in a non-valvular location. Autosomal-dominant polycystic kidney disease (ADPKD) typically presents with multiple bilateral renal cysts, resulting in chronic kidney disease. Whilst many of the extra-renal manifestations of ADPKD are well-documented, associated cardiac masses are extremely rare: and cardiac blood cyst has not been...
• Whole exome sequencing identifies monogenic forms of nephritis in a previously unsolved cohort of children with steroid-resistant nephrotic syndrome and hematuria
  CONCLUSIONS: We confirmed that in cohorts of childhood-onset SRNS, patients with nephritic syndrome can be discerned by WES. The findings highlight the importance of clinical genetic testing for therapeutic and preventative measures in patients with proteinuria. A higher resolution version of the Graphical abstract is available as Supplementary information.
• Electrophysiological Recordings of the Polycystin Complex in the Primary Cilium of Cultured Mouse IMCD-3 Cell Line
  PC-1 and PC-2 form an ion channel complex called the polycystin complex, which predominantly localizes to a small hair-like organelle called the primary cilium. The polycystin complex permeates cations, K^(+), Na^(+), and Ca^(2+), and has an unusual 1:3 stoichiometry that combines one PC-1 subunit with three PC-2 subunits. However, the small size and shape of primary cilia impose technical challenges to study the polycystin complex in its native environment. In this paper, we describe the...
• A case of Bardet-Biedl syndrome caused by a recurrent variant in BBS12: A case report
  Bardet-Biedl syndrome (BBS) is a clinically and genetically heterogenous disorder that manifests as a result of primary cilia impairment. Cilia are present on most cell types, thus BBS is a multisystemic condition involving the majority of organ systems. The core features of the syndrome include retinal degeneration, obesity, polydactyly, cognitive impairment, renal anomalies and urogenital malformations. To date, pathogenic variants in 26 genes have been shown to be involved in the molecular...
• Compound heterozygous ADAMTS9 variants in Joubert syndrome-related disorders without renal manifestation
  CONCLUSIONS: The case suggested a possible association between the clinical presentation of JSRD and ADAMTS9-related disease, and it shows a wide spectrum of ADAMTS9 phenotype.
• Editorial: The Cytoskeleton and Cellular Compartmentation: Cilia as Specialized Cellular Domains
  No abstract
• Hepatic Ciliopathy Syndromes
  Content available: Author Interview and Audio Recording.
• Role of Primary Cilia in Bone and Cartilage
  The primary cilium is a nonmotile microtubule-based organelle in most vertebrate cell types. The primary cilium plays a critical role in tissue development and homeostasis by sensing and transducing various signaling pathways. Ciliary proteins such as intraflagellar transport (IFT) proteins as well as ciliary motor proteins, kinesin and dynein, comprise a bidirectional intraflagellar transport system needed for cilia formation and function. Mutations in ciliary proteins that lead to loss or...