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dc.contributor.authorOhishi, Yuta
dc.contributor.authorAmmann, Sandra
dc.contributor.authorZiaee, Vahid
dc.contributor.authorStrege, Katharina
dc.contributor.authorGroß, Miriam
dc.contributor.authorAmos, Carla Vazquez
dc.contributor.authorShahrooei, Mohammad
dc.contributor.authorAshournia, Parisa
dc.contributor.authorRazaghian, Anahita
dc.contributor.authorGriffiths, Gillian M.
dc.contributor.authorEhl, Stephan
dc.contributor.authorFukuda, Mitsunori
dc.contributor.authorParvaneh, Nima
dc.date.accessioned2020-12-24T05:04:14Z
dc.date.available2020-12-24T05:04:14Z
dc.date.issued2020-12-10
dc.date.submitted2020-10-01
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/315588
dc.description.abstractGriscelli syndrome type 2 (GS-2) is an inborn error of immunity characterized by partial albinism and episodes of hemophagocytic lymphohistiocytosis (HLH). It is caused by RAB27A mutations that encode RAB27A, a member of the Rab GTPase family. RAB27A is expressed in many tissues and regulates vesicular transport and organelle dynamics. Occasionally, GS-2 patients with RAB27A mutation display normal pigmentation. The study of such variants provides the opportunity to map distinct binding sites for tissue-specific effectors on RAB27A. Here we present a new case of GS-2 without albinism (GS-2 sine albinism) caused by a novel missense mutation (Val143Ala) in the RAB27A and characterize its functional cellular consequences. Using pertinent animal cell lines, the Val143Ala mutation impairs both the RAB27A–SLP2-A interaction and RAB27A–MUNC13-4 interaction, but it does not affect the RAB27A–melanophilin (MLPH)/SLAC2-A interaction that is crucial for skin and hair pigmentation. We conclude that disruption of the RAB27A–MUNC13-4 interaction in cytotoxic lymphocytes leads to the HLH predisposition of the GS-2 patient with the Val143Ala mutation. Finally, we include a review of GS-2 sine albinism cases reported in the literature, summarizing their genetic and clinical characteristics.
dc.languageen
dc.publisherFrontiers Media S.A.
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectImmunology
dc.subjectGriscelli syndrome type 2 sine albinism
dc.subjectwhole-exome sequencing
dc.subjecthemophagocytic lymphohistiocytosis
dc.subjectRAB27A
dc.subjectMLPH/SLAC2-A
dc.subjectMUNC13-4
dc.subjectinborn error of immunity
dc.titleGriscelli Syndrome Type 2 Sine Albinism: Unraveling Differential RAB27A Effector Engagement
dc.typeArticle
dc.date.updated2020-12-24T05:04:13Z
prism.publicationNameFrontiers in Immunology
prism.volume11
dc.identifier.doi10.17863/CAM.62694
dcterms.dateAccepted2020-11-03
rioxxterms.versionofrecord10.3389/fimmu.2020.612977
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.identifier.eissn1664-3224


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)