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.

Some of the papers are free to read; others require subscriptions.

25 October 2021

  • Multiallelic Rare Variants in BBS Genes Support an Oligogenic Ciliopathy in a Non-obese Juvenile-Onset Syndromic Diabetic Patient: A Case Report
    Juvenile-onset diabetes may occur in the context of a rare syndromic presentation, suggesting a monogenic etiology rather than a common multifactorial diabetes. In the present study, we report the case of a young diabetic Tunisian patient presenting learning problems, speech deficits, short stature, brachydactyly, and a normal weight. Whole exome sequencing analysis revealed five heterozygous genetic variants in BBS1, BBS4, BBS8, MKS1, and CEP290. These genes are involved in the regulation of...
  • Overexpression of smad7 inhibits the TGF-β/Smad signaling pathway and EMT in NPHP1-defective MDCK cells
    CONCLUSIONS: Our results indicate that NPHP1 defects induce the activation of the TGF-β/Smad signaling pathway and EMT in MDCK cells. These factors may be implicated in the pathogenesis of interstitial fibrosis in NPHP.
  • Magnetically Assisted Drug Delivery of Topical Eye Drops Maintains Retinal Function In Vivo in Mice
    Barded-Biedl syndrome (BBS) is a rare genetic disorder with an unmet medical need for retinal degeneration. Small-molecule drugs were previously identified to slow down the apoptosis of photoreceptors in BBS mouse models. Clinical translation was not practical due to the necessity of repetitive invasive intravitreal injections for pediatric populations. Non-invasive methods of retinal drug targeting are a prerequisite for acceptable adaptation to the targeted pediatric patient population. Here,...
  • MicroRNA-124 Alleviates Retinal Vasoregression via Regulating Microglial Polarization
    Microglial activation is implicated in retinal vasoregression of the neurodegenerative ciliopathy-associated disease rat model (i.e., the polycystic kidney disease (PKD) model). microRNA can regulate microglial activation and vascular function, but the effect of microRNA-124 (miR-124) on retinal vasoregression remains unclear. Transgenic PKD and wild-type Sprague Dawley (SD) rats received miR-124 at 8 and 10 weeks of age intravitreally. Retinal glia activation was assessed by immunofluorescent...
  • Using Paramecium as a Model for Ciliopathies
    Paramecium has served as a model organism for the studies of many aspects of genetics and cell biology: non-Mendelian inheritance, genome duplication, genome rearrangements, and exocytosis, to name a few. However, the large number and patterning of cilia that cover its surface have inspired extraordinary ultrastructural work. Its swimming patterns inspired exquisite electrophysiological studies that led to a description of the bioelectric control of ciliary motion. A genetic dissection of...
  • Molecular Diagnosis and Prenatal Phenotype Analysis of Eight Fetuses With Ciliopathies
    Human ciliopathies are hereditary conditions caused by variants in ciliary-associated genes. Ciliopathies are often characterized by multiple system defects. However, it is not easy to make a definite diagnosis in the prenatal period only based on the imageology. In this report, eight new prenatal cases from five unrelated families diagnosed with ciliopathies were systematically examined. The clinical manifestations of these fetuses showed such prenatal diagnostic features as occipital...
  • SUFU haploinsufficiency causes a recognisable neurodevelopmental phenotype at the mild end of the Joubert syndrome spectrum
    CONCLUSION: Heterozygous truncating or splice-site SUFU variants cause a novel neurodevelopmental syndrome encompassing COMA and mild JS, which likely represent overlapping entities. Variants can arise de novo or be inherited from a healthy parent, representing the first cause of JS with dominant inheritance and reduced penetrance. Awareness of this condition will increase the diagnostic yield of JS genetic testing, and allow appropriate counselling about prognosis, medical monitoring and...
  • Another Piece of the Puzzle of Anomalous Connectivity in Joubert's Syndrome
    We report on the conventional and diffusion tensor imaging (DTI) findings of a 2-year-old child with clinical presentation of Joubert's Syndrome (JS) and brainstem structural abnormalities as depicted by neuroimaging.Conventional magnetic resonance imaging (MRI) showed a "molar tooth" configuration of the brainstem. A band-like formation coursing in an apparent axial plane anterior to the interpeduncular fossa was noted and appeared to partially cover the interpeduncular fossa.DTI maps and...
  • Ciliary Hedgehog signaling regulates cell survival to build the facial midline
    Craniofacial defects are among the most common phenotypes caused by ciliopathies, yet the developmental and molecular etiology of these defects is poorly understood. We investigated multiple mouse models of human ciliopathies (including Tctn2, Cc2d2a and Tmem231 mutants) and discovered that each displays hypotelorism, a narrowing of the midface. As early in development as the end of gastrulation, Tctn2 mutants displayed reduced activation of the Hedgehog (HH) pathway in the prechordal plate, the...
  • Whole genome sequencing in transposition of the great arteries and associations with clinically relevant heart, brain and laterality genes.: WGS in transposition of the great arteries
    CONCLUSION: We present compelling evidence that the majority of TGA is not caused by monogenic rare variants and is most likely oligogenic and/or polygenic in nature, highlighting the complex genetic architecture and multifactorial influences on this CHD sub-type and its long-term sequelae. Assessment of variant burden in key heart, brain and/or laterality genes may be required to unravel the genetic contributions to TGA and related disabilities.
  • Repetitive Refractory Renal Cyst Infection in Autosomal Dominant Polycystic Kidney Disease for which Renal Transcatheter Arterial Embolization Was Effective in Preventing Recurrence
    Renal cyst infection is a frequent and serious complication of autosomal dominant polycystic kidney disease (ADPKD) that is often difficult to treat and can be fatal. While nephrectomy is the standard therapy for severe refractory renal cyst infection, it can be associated with severe adverse events. We experienced a case of repetitive renal cyst infection in a 58-year-old Japanese man with ADPKD on dialysis. He underwent renal transcatheter arterial embolization (TAE) four months after the last...
  • Loss of the ciliary gene Bbs4 results in defective thermogenesis due to metabolic inefficiency and impaired lipid metabolism
    Adipose tissue is central to the regulation of energy balance. While white adipose tissue (WAT) is responsible for triglyceride storage, brown adipose tissue specializes in energy expenditure. Deterioration of brown adipocyte function contributes to the development of metabolic complications like obesity and diabetes. These disorders are also leading symptoms of the Bardet-Biedl syndrome (BBS), a hereditary disorder in humans which is caused by dysfunctions of the primary cilium and which...
  • INTU-related oral-facial-digital syndrome XVII: Clinical spectrum of a rare disorder
    Oral-facial-digital syndromes (OFDSs) as a subgroup of ciliopathies are rare genetic disorders characterized by the association of abnormalities of the face, oral cavity, and extremities. OFDS XVII is a recently described subtype of OFDS that presents with developmental delay, facial dysmorphism, high palate, tongue nodules, brain malformations, cardiac anomaly, polydactyly, renal malformation, and various other findings. OFDS XVII is caused by biallelic variants in INTU gene and is inherited...
  • An updated SYSCILIA gold standard (SCGSv2) of known ciliary genes, revealing the vast progress that has been made in the cilia research field
    Cilia are microtubule-based organelles with important functions in motility and sensation. They contribute to a broad spectrum of developmental disorders called ciliopathies, and have recently been linked to common conditions such as cancers and congenital heart disease. There has been increasing interest in the biology of cilia and their contribution to disease over the past two decades. As a result, in 2013 we published a 'Gold Standard' list of genes confirmed to be associated with cilia....
  • Wdr47, Camsaps, and Katanin cooperate to generate ciliary central microtubules
    The axonemal central pair (CP) are non-centrosomal microtubules critical for planar ciliary beat. How they form, however, is poorly understood. Here, we show that mammalian CP formation requires Wdr47, Camsaps, and microtubule-severing activity of Katanin. Katanin severs peripheral microtubules to produce central microtubule seeds in nascent cilia. Camsaps stabilize minus ends of the seeds to facilitate microtubule outgrowth, whereas Wdr47 concentrates Camsaps into the axonemal central lumen to...
  • Fetal ciliopathies: a retrospective observational single-center study
    CONCLUSION: Prenatal detection of renal abnormalities associated with skeletal or brain abnormalities should raise the suspicion for multisystem ciliopathies. Prenatal ultrasound can help to differentiate between different diseases and pave the way for subsequent targeted genetic testing.
  • Cilia kinases in skeletal development and homeostasis
    Primary cilia are dynamic compartments that regulate multiple aspects of cellular signaling. The production, maintenance, and function of cilia involve more than 1000 genes in mammals, and their mutations disrupt the ciliary signaling which manifests in a plethora of pathological conditions-the ciliopathies. Skeletal ciliopathies are genetic disorders affecting the development and homeostasis of the skeleton, and encompass a broad spectrum of pathologies ranging from isolated polydactyly to...
  • Bardet-Biedl syndrome proteins modulate the release of bioactive extracellular vesicles
    Primary cilia are microtubule based sensory organelles important for receiving and processing cellular signals. Recent studies have shown that cilia also release extracellular vesicles (EVs). Because EVs have been shown to exert various physiological functions, these findings have the potential to alter our understanding of how primary cilia regulate specific signalling pathways. So far the focus has been on lgEVs budding directly from the ciliary membrane. An association between cilia and...
  • The Role of Sonic Hedgehog in Human Holoprosencephaly and Short-Rib Polydactyly Syndromes
    The Hedgehog (HH) signalling pathway is one of the major pathways controlling cell differentiation and proliferation during human development. This pathway is complex, with HH function influenced by inhibitors, promotors, interactions with other signalling pathways, and non-genetic and cellular factors. Many aspects of this pathway are not yet clarified. The main features of Sonic Hedgehog (SHH) signalling are discussed in relation to its function in human development. The possible role of SHH...
  • Current and Future Treatments in Primary Ciliary Dyskinesia
    Primary ciliary dyskinesia (PCD) is a rare genetic ciliopathy in which mucociliary clearance is disturbed by the abnormal motion of cilia or there is a severe reduction in the generation of multiple motile cilia. Lung damage ensues due to recurrent airway infections, sometimes even resulting in respiratory failure. So far, no causative treatment is available and treatment efforts are primarily aimed at improving mucociliary clearance and early treatment of bacterial airway infections. Treatment...
  • Ciliary Videomicroscopy: A Long Beat from the European Respiratory Society Guidelines to the Recognition as a Confirmatory Test for Primary Ciliary Dyskinesia
    Primary ciliary dyskinesia (PCD) is a rare inherited ciliopathy in which respiratory cilia are stationary or dyskinetic. The clinical presentation of PCD is highly non-specific since it includes infections and disorders of the upper (otitis and rhinosinusitis) and lower (neonatal respiratory distress, bronchitis, pneumonia and bronchiectasis) airways, starting in early life. Clinical examination alone does not allow a PCD diagnosis, which relies on several concordant tests, since none are...