Autosomal Recessive Keratoderma-Ichthyosis-Deafness (ARKID) Syndrome Is Caused by VPS33B Mutations Affecting Rab Protein Interaction and Collagen Modification

Gruber, Robert; Rogerson, Clare; Windpassinger, Christian; Banushi, Blerida; Straatman-Iwanowska, Anna; Hanley, Joanna; Forneris, Federico; Strohal, Robert; Ulz, Peter; Crumrine, Debra; Menon, Gopinathan K.; Blunder, Stefan; Schmuth, Matthias; Müller, Thomas; Smith, H. R.; Mills, Kevin; Kroisel, Peter M.; Janecke, Andreas; Gissen, Paul

doi:10.1016/j.jid.2016.12.010

Cited by 36 publications

(52 citation statements)

References 42 publications

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“…Fourteen percent of patients with syndromic ichthyoses were diagnosed as having ARKID syndrome, a recently described entity [39]. This might indicate that the phenotype was previously unrecognized.…”

Section: Discussionmentioning

confidence: 99%

Spectrum of ichthyoses in an Austrian ichthyosis cohort from 2004 to 2017

Seidl‐Philipp

Schatz

Gasslitter

et al. 2019

J Deutsche Derma Gesell

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Summary Background Ichthyoses are a heterogeneous disease group, which makes clinical classification challenging. An ichthyosis cohort at a center for genodermatoses is presented in detail. Patients and Methods Patients with clinically and/or genetically confirmed ichthyosis seen from 2004 to 2017 and listed in a database were included. Disease onset, phenotype, histology, comorbidities and family history were described in detail. In genetically tested patients, the prevalence of various ARCI genes, ARCI phenotypes and syndromic ichthyoses, as well as genotype‐phenotype correlation and year/method of genetic testing was assessed. Results Of all 198 patients who were included in the cohort, 151 were genetically tested. 81 had ichthyosis vulgaris, 43 X‐linked ichthyosis, 38 autosomal recessive congenital ichthyosis (ARCI), 9 keratinopathic ichthyosis (KPI) and one exfoliative ichthyosis. 26 individuals suffered from syndromic ichthyoses. A good genotype‐phenotype correlation was observed for common ichthyoses and KPI; the correlation was less good in syndromic ichthyoses. In 91 % of ARCI patients an accurate diagnosis was obtained by genetic testing. In only 33 % of syndromic ichthyoses was the definitive diagnosis suspected before genetic testing, which revealed a causative mutation in 86 % of cases. Conclusion This study describes the spectrum of ichthyoses in a center of expertise and shows that genetic testing should become a diagnostic standard for this disease group.

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Section: Discussionmentioning

confidence: 99%

Spectrum of ichthyoses in an Austrian ichthyosis cohort from 2004 to 2017

Seidl‐Philipp

Schatz

Gasslitter

et al. 2019

J Deutsche Derma Gesell

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“…This provides an explanation for the ARC symptoms affecting the kidney and platelet cells. A missense mutation in VPS33B that affects its interaction with Rab proteins results in a milder condition called a utosomal‐ r ecessive k eratoderma‐ i chthyosis‐ d eafness (ARKID) syndrome . The patients present severe palmoplantar keratoderma associated with ichthyosis and sensorineural deafness.…”

Section: Intercellular Lipid Lamellae and Lamellar Granulesmentioning

confidence: 99%

Molecular basis of the skin barrier structures revealed by electron microscopy

Ishida‐Yamamoto

Igawa

Kishibe

2018

Experimental Dermatology

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The barrier function of skin is indispensable for terrestrial animals. This function is mainly carried out by the epidermis, more specifically by its granular and cornified layers. The major structural components associated with this function are the intercellular lipid layer, desmosomes, corneodesmosomes, tight junctions, cornified cell envelope and keratin filaments. In this review, we discuss the current knowledge of their ultrastructure, their molecular basis and their relevance to skin disease.

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“…However, there is evidence of evolutionary divergence within the membrane trafficking system. Metazoan VPS33A and VPS33B are both homologs of the yeast HOPS subunit Vps33 (17), but only VPS33A is found in human HOPS (6,11,18) and mutations in these two homologs generate significantly different phenotypes (19)(20)(21)(22)(23). Also, Vps41 in yeast has been shown to bind directly to Ypt7 (24), but in humans it appears that the analogous interaction (with Rab7) is mediated by an additional protein, RILP (14).…”

Section: Introductionmentioning

confidence: 99%

VPS18 recruits VPS41 to the human HOPS complex via a RING-RING interaction

Hunter

Scourfield

Emmott

et al. 2017

Preprint

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The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/169185 doi: bioRxiv preprint first posted online 2 ABSTRACT Eukaryotic cells use conserved multisubunit membrane tethering complexes, including CORVET and HOPS, to control the fusion of endomembranes. These complexes have been extensively studied in yeast, but to date there have been far fewer studies of metazoan CORVET and HOPS. Both of these complexes comprise six subunits: a common four-subunit core and two unique subunits. Once assembled, these complexes function to recognise specific endosomal membrane markers and facilitate SNARE-mediated membrane fusion.CORVET promotes the homotypic fusion of early endosomes, while HOPS promotes the fusion of lysosomes to late endosomes and autophagosomes. Many of the subunits of both CORVET and HOPS contain putative C-terminal zinc-finger domains. Here, the contribution of these domains to the assembly of the human CORVET and HOPS complexes has been examined. Using biochemical techniques, we demonstrate that the zinc-containing RING domains of human VPS18 and VPS41 interact directly to form a stable heterodimer. In cells, these RING domains are able to integrate into endogenous HOPS, showing that the VPS18 RING domain is required to recruit VPS41 to the core complex subunits. Importantly, this mechanism is not conserved throughout eukaryotes, as yeast Vps41 does not contain a C-terminal zinc-finger motif. The subunit analogous to VPS41 in human CORVET is VPS8, in which the RING domain has an additional C-terminal segment that is predicted to be disordered. Both the RING and disordered C-terminal domains are required for integration of VPS8 into endogenous CORVET complexes, suggesting that HOPS and CORVET recruit VPS41 and VPS8 via distinct molecular interactions.

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Autosomal Recessive Keratoderma-Ichthyosis-Deafness (ARKID) Syndrome Is Caused by VPS33B Mutations Affecting Rab Protein Interaction and Collagen Modification

Cited by 36 publications

References 42 publications

Spectrum of ichthyoses in an Austrian ichthyosis cohort from 2004 to 2017

Spectrum of ichthyoses in an Austrian ichthyosis cohort from 2004 to 2017

Molecular basis of the skin barrier structures revealed by electron microscopy

VPS18 recruits VPS41 to the human HOPS complex via a RING-RING interaction

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