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dc.contributor.authorIRVINE, ALANen
dc.date.accessioned2015-11-11T11:12:53Z
dc.date.available2015-11-11T11:12:53Z
dc.date.issued2012en
dc.date.submitted2012en
dc.identifier.citationPohler E, Mamai O, Hirst J, Zamiri M, Horn H, Nomura T, Irvine AD, Moran B, Wilson NJ, Smith FJ, Goh CS, Sandilands A, Cole C, Barton GJ, Evans AT, Shimizu H, Akiyama M, Suehiro M, Konohana I, Shboul M, Teissier S, Boussofara L, Denguezli M, Saad A, Gribaa M, Dopping-Hepenstal PJ, McGrath JA, Brown SJ, Goudie DR, Reversade B, Munro CS, McLean WH, Haploinsufficiency for AAGAB causes clinically heterogeneous forms of punctate palmoplantar keratoderma., Nature genetics, 44, 11, 2012, 1272-6en
dc.identifier.issn1061-4036en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/74865
dc.descriptionPUBLISHEDen
dc.description.abstractPalmoplantar keratodermas (PPKs) are a group of disorders that are diagnostically and therapeutically problematic in dermatogenetics. Punctate PPKs are characterized by circumscribed hyperkeratotic lesions on the palms and soles with considerable heterogeneity. In 18 families with autosomal dominant punctate PPK, we report heterozygous loss-of-function mutations in AAGAB, encoding α- and γ-adaptin-binding protein p34, located at a previously linked locus at 15q22. α- and γ-adaptin-binding protein p34, a cytosolic protein with a Rab-like GTPase domain, was shown to bind both clathrin adaptor protein complexes, indicating a role in membrane trafficking. Ultrastructurally, lesional epidermis showed abnormalities in intracellular vesicle biology. Immunohistochemistry showed hyperproliferation within the punctate lesions. Knockdown of AAGAB in keratinocytes led to increased cell division, which was linked to greatly elevated epidermal growth factor receptor (EGFR) protein expression and tyrosine phosphorylation. We hypothesize that p34 deficiency may impair endocytic recycling of growth factor receptors such as EGFR, leading to increased signaling and cellular proliferationen
dc.format.extent1272-6en
dc.relation.ispartofseriesNature geneticsen
dc.relation.ispartofseries44en
dc.relation.ispartofseries11en
dc.rightsYen
dc.subjectPalmoplantar keratodermas (PPKs)en
dc.titleHaploinsufficiency for AAGAB causes clinically heterogeneous forms of punctate palmoplantar keratoderma.en
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/irvineaen
dc.identifier.rssinternalid83565en
dc.identifier.doihttp://dx.doi.org/10.1038/ng.2444en
dc.rights.ecaccessrightsopenAccess
dc.subject.TCDThemeImmunology, Inflammation & Infectionen
dc.identifier.orcid_id0000-0002-9048-2044en


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