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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17 April 2023
- Aberrant centrosome biogenesis disrupts nephron progenitor cell renewal and fate resulting in fibrocystic kidney disease
Mutations that disrupt centrosome structure or function cause congenital kidney developmental defects and fibrocystic pathologies. Yet, it remains unclear how mutations in proteins essential for centrosome biogenesis impact embryonic kidney development. Here, we examined the consequences of conditional deletion of a ciliopathy gene, Cep120 , in the two nephron progenitor niches of the embryonic kidney. Cep120 loss led to reduced abundance of both metanephric mesenchyme and ureteric bud...
- Impaired centrosome biogenesis in kidney stromal progenitors reduces abundance of interstitial lineages and accelerates injury-induced fibrosis
Defective centrosome function can disrupt embryonic kidney development, by causing changes to the renal interstitium that leads to fibrocystic disease pathologies. Yet, it remains unknown how mutations in centrosome genes impact kidney interstitial cells. Here, we examined the consequences of defective centrosome biogenesis on stromal progenitor cell growth, differentiation and fate. Conditional deletion of Cep120 , a ciliopathy gene essential for centrosome duplication, in the stromal...
- Neuronal primary cilia integrate peripheral signals with metabolic drives
Neuronal primary cilia have recently emerged as important contributors to the central regulation of energy homeostasis. As non-motile, microtubule-based organelles, primary cilia serve as signaling antennae for metabolic status. The impairment of ciliary structure or function can produce ciliopathies for which obesity is a hallmark phenotype and global ablation of cilia induces non-syndromic adiposity in mouse models. This organelle is not only a hub for metabolic signaling, but also for...
- Molecular genetic diagnosis of kidney ciliopathies: Lessons from interpreting genomic sequencing data and the requirement for accurate phenotypic data
CONCLUSION: This case illustrates that reanalysis of WGS data in unsolved cases of cystic kidney disease is valuable. Clinical phenotypes must be reassessed as these may have been incorrectly recorded and evolve over time. Undertaking additional studies including genotype-phenotype correlation in wider family members provides useful diagnostic information.
- Xanthogranulomatous pyelonephritis with polycystic kidney disease as a mimic of cystic renal cell carcinoma: a case report
CONCLUSIONS: XGP should be kept in mind during the differential diagnosis of renal masses with ADPKD even in the absence of characteristic clinical symptoms and imaging manifestations.
- Disease modeling of ADAMTS9-related nephropathy using kidney organoids reveals its roles in tubular cells and podocytes
CONCLUSIONS: Mutations in ADMATS9 cause a glomerulotubular nephropathy in kidney and our study provides insights into the functional roles of ADMATS9 in glomeruli and tubules.
- Phenotypic diversity observed in a Chinese patient cohort with biallelic variants in Bardet-Biedl syndrome genes
CONCLUSIONS: Our study defined the mutated gene profiles and established the configuration of the variation frequencies for each BBS gene in Chinese patients. Overall, our patients showed early and severe visual defects and retinal degeneration. Genetic analysis is therefore crucial for diagnosis, genetic counseling, and future gene therapy in these patients.
- Editorial: Signaling by primary cilia in development and disease
- Computational study of biomechanical drivers of renal cystogenesis
Renal cystogenesis is the pathological hallmark of autosomal dominant polycystic kidney disease, caused by PKD1 and PKD2 mutations. The formation of renal cysts is a common manifestation in ciliopathies, a group of syndromic disorders caused by mutation of proteins involved in the assembly and function of the primary cilium. Cystogenesis is caused by the derailment of the renal tubular architecture and tissue deformation that eventually leads to the impairment of kidney function. However, the...
- Probenecid slows disease progression in a murine model of autosomal dominant polycystic kidney disease
Development of autosomal dominant polycystic kidney disease (ADPKD) involves renal epithelial cell abnormalities. Cystic fluid contains a high level of ATP that, among other effects, leads to a reduced reabsorption of electrolytes in cyst-lining cells, and thus results in cystic fluid accumulation. Earlier, we demonstrated that Pkd1^(RC/RC) mice, a hypomorphic model of ADPKD, exhibit increased expression of pannexin-1, a membrane channel capable of ATP release. In the current study, we found...
- Combining Panel-Based Next-Generation Sequencing and Exome Sequencing for Genetic Liver Diseases
CONCLUSIONS: NGS based genetic test using a combined panel-WES approach is efficient for the diagnosis of the highly diverse genetic liver diseases.
- The actin-bundling protein Fascin-1 modulates ciliary signalling
Primary cilia are microtubule-based cell organelles important for cellular communication. Since they are involved in the regulation of numerous signalling pathways, defects in cilia development or function are associated with genetic disorders, collectively called ciliopathies. Besides their ciliary functions, recent research has shown that several ciliary proteins are involved in the coordination of the actin cytoskeleton. Although ciliary and actin phenotypes are related, the exact nature of...
- Ciliopathies in pediatric endocrinology
Ciliopathies are a group of disorders that involve many organs and systems. In this review, we consider the role of the cilium in multiorgan pathology with a focus on endocrinological aspects. Identification of new genes and mutations is the major challenge in development of a tailored and appropriate therapy. It is expected that new mutations will be identified to characterize ciliopathies and promote new therapies.
- An evaluation of setmelanotide injection for chronic weight management in adult and pediatric patients with obesity due to Bardet-Biedl syndrome
INTRODUCTION: Bardet-Biedl Syndrome (BBS) is a rare, multisystemic ciliopathy with an incidence of obesity of 89%. Mutations in genes encoding BBS proteins are linked to reduced leptin sensitivity of hypothalamic POMC neurons and reduced activation of the melanocortin-4 receptor (MC4R) pathway due to deficient α-MSH production by hypothalamic POMC neurons. The MC4R pathway is involved in controlling body weight and energy metabolism, and its disruption is linked to hyperphagia and obesity....
- Shift from severe hypotension to salt-dependent hypertension in a child with autosomal recessive polycystic kidney disease after bilateral nephrectomies: a case report
CONCLUSIONS: Our case report illustrates an unusual course of blood pressure changes following bilateral nephrectomies in an infant with ARPKD and the particular importance of tight regulation of sodium chloride supplementation. The case adds to the scarce literature about clinical sequences of bilateral nephrectomies in infants, and as well highlights the challenge of managing blood pressure in these patients. Further research on the mechanisms and management of blood pressure control is...
- Calcineurin associates with centrosomes and regulates cilia length maintenance
Calcineurin, or PP2B, the Ca2+ and calmodulin-activated phosphatase and target of immunosuppressants, has many substrates and functions that remain undiscovered. By combining rapid proximity-dependent labeling with cell cycle synchronization, we mapped the spatial distribution of calcineurin in different cell cycle stages. While calcineurin-proximal proteins did not vary significantly between interphase and mitosis, calcineurin consistently associated with multiple centrosomal/ciliary proteins....
- Novel multi-allelic variants, two BBS2 and one PKD1 variant, of renal ciliopathies: A case report and literature review
CONCLUSION: This paper reported a ciliopathy patient with multi-allelic variants (two BBS2 variants and one PKD1 variant) that may lead to early symptoms and more rapid progression. An early genetic diagnosis may contribute to predicting disease progression and guiding management and follow-up.
- Mucus Plugging in Primary Ciliary Dyskinesia
- The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion
Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent potentially lethal monogenic disorder. Mutations in the PKD1 gene, which encodes polycystin-1 (PC1), account for approximately 78% of cases. PC1 is a large 462-kDa protein that undergoes cleavage in its N and C-terminal domains. C-terminal cleavage produces fragments that translocate to mitochondria. We show that transgenic expression of a protein corresponding to the final 200 amino acid (aa) residues of PC1 in two...
- Complex PKD1 Genetics in Early-Onset Cystic Kidney Disease
- Cholesterol and Phosphoinositides in Cilia Biology
Cilia are evolutionarily conserved organelles that can be found on virtually every cell. They appear as hair-like structures emanating from the cellular surface either as single or as bundles of cilia. There, they sense external stimuli and translate them into intracellular signals. Motile cilia beat for the generation of locomotion of unicellular organisms or fluid flow in certain body cavities of vertebrate organisms. Defects in cilia are detrimental and account for the development of...