VPS33B and VIPAR are essential for epidermal lamellar body biogenesis and function
Publication date: May 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 5, Part A Author(s): Clare Rogerson, Paul Gissen Mutations in VPS33B and VIPAS39 cause the severe multisystem disorder Arthrogryposis, Renal dysfunction and Cholestasis (ARC) syndrome. Amongst other symptoms, patients with ARC syndrome suffer from severe ichthyosis. Roles for VPS33B and VIPAR have been reported in lysosome-related organelle biogenesis, integrin recycling, collagen homeostasis and maintenance of cell polarity. Mouse knockouts of Vps33b or Vipas39 are good models of ARC syndrome and develop an ichthyotic phenotype. We demonstrate that the skin manifestations in Vps33b and Vipar deficient mice are histologically similar to those of patients with ARC syndrome. Histological, immunofluorescent and electron microscopic analysis of Vps33b and Vipar deficient mouse skin biopsies and isolated primary cells showed that epidermal lamellar bodies, which are essential for skin barrier function, had abnormal morphology and the localisation of lamellar body cargo was disrupted. Stratum corneum formation was affected, with increased corneocyte thickness, decreased thickness of the cornified envelope and reduced deposition of lipids. These defects impact epidermal homeostasis and lead to abnormal barrier formation causing the skin phenotype in Vps33b and Vipar deficient mice and patients with ARC syndrome.
CONCLUSION: The presented optical procedures provide valuable additional information that supports dermatologists in making the correct diagnosis. However, a surgical biopsy followed by dermatohistopathological examination remains the diagnostic gold standard in dermatology. PMID: 31965207 [PubMed - as supplied by publisher]
CONCLUSIONS: While the use of CAP for disinfection and wound treatment has already moved into clinical practice, further applications such as cancer treatment are still exploratory. PMID: 31965204 [PubMed - as supplied by publisher]
Conclusions: Infants with IFALD treated with FOLE showed comparable somatic growth to those treated with SOLE in early infancy, and improved somatic growth up to 24 months of age, supporting its wider use in this patient population.
Abstract A 37-year-old male patient, Fitzpatrick skin phototype IV, a student living in Belem, Amazon region, in 2015 had a confirmed diagnosis of acquired immunodeficiency virus (HIV) infection, but did not initiate antiretroviral treatment at his own option. Three years after the diagnosis, erythematous maculae appeared on the dorsum of the nose with rapid progression to the entire face, with posterior diffuse infiltration and appearance of nodules on the chin and shoulder. In December 2018, the patient presented with exacerbation of the condition with an increase in infiltrated violaceous plaques and disseminat...
Journal Name: Drug Metabolism and Personalized Therapy Issue: Ahead of print
We report on the case of a 2-year-old boy from a consanguineous Moroccan family, presenting with NISCH syndrome and carrying the so-called Moroccan homozygous mutation (c.200-201delTT). The patient presented with the characteristic symptoms of the syndrome and a favorable progression with normalization of hepatic analyses under symptomatic treatment (vitamin supplementation and ursodeoxycholic acid). The currently limited availability of clinical and therapeutic data does not allow accurate prediction of the course of the disease and short- and long-term prognosis. Moreover, substantial interindividual variability has been...
Three Austrian patients presented with severe palmoplantar keratoderma associated with ichthyosis and sensorineural deafness. Exome sequencing revealed biallelic mutations in VPS33B, encoding VPS33B, a Sec1/Munc18 family protein which interacts with Rab11a and Rab25 proteins and is involved in trafficking of the collagen modifying enzyme LH3. Two patients showed the homozygous missense variant p.Gly131Glu, whilst one patient was compound heterozygous for p.Gly131Glu and the splice site mutation c.240-1G>C, previously reported in patients with arthrogryposis renal dysfunction and cholestasis syndrome.
Mutations in Vps33b and Vipas39 cause the rare multisystem disorder Arthrogryposis, Renal dysfunction and Cholestasis syndrome (ARC); one characteristic but understudied feature of which is severe ichthyosis. The Vps33b and Vipar proteins interact and have been shown to also interact with Rab GTPases and act as a tethering factor; the class C Homologues in Endosome-Vesicle Interaction (CHEVI) complex. ARC syndrome patients have been shown to have entombed lamellar body-like structures in the stratum corneum however the molecular mechanisms underlying ARC patient ichthyosis and the specific role of the CHEVI complex in the ...
Publication date: Available online 17 February 2017 Source:Pediatria Polska Author(s): Patryk Lipiński, Irena Jankowska Cholestatic liver diseases remain a major clinical issue for pediatricians. The article constitutes an up-to-day overview on cholestasis with elevated serum gamma-glutamyl transpeptidase activity. Authors presented the pathogenicity, clinical presentation, biochemical and molecular diagnostics of the following disorders: progressive familial intrahepatic cholestasis type 3, adenosine kinase deficiency, neonatal ichthyosis – sclerosing cholangitis syndrome.