title: Unusual functional manifestations of a novel STX11 frameshift mutation in two infants with familial hemophagocytic lymphohistiocytosis type 4 (FHL4).
abstract: Familial hemophagocytic lymphohistiocytosis (FHL) is typically an autosomal recessive, early-onset, life-threatening immune disorder. Loss-of-function mutations in STX11 have been found to impair NK cell degranulation and cytotoxicity. Here, we describe two unrelated infants of Punjabi descent presenting with FHL and carrying a novel, homozygous STX11 frameshift mutation [c.867dupG]. Western blot analysis indicated absence of syntaxin-11. Unexpectedly, degranulation by NK cells from one of the patients was not impaired, although patient NK cells showed mildly and significantly decreased cytotoxicity, respectively. Importantly, these observations imply that STX11 should be sequenced in HLH patients even when impaired NK cell degranulation is not found.
authors.affiliation: The Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Macartney
authors.forename: Sheila
authors.initials: S
authors.lastname: Weitzman
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Wood
authors.forename: Deepak
authors.initials: D
authors.lastname: Bansal
authors.forename: Macgregor
authors.initials: M
authors.lastname: Steele
authors.forename: Marie
authors.initials: M
authors.lastname: Meeths
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdelhaleem
authors.forename: Yenan T
authors.initials: YT
authors.lastname: Bryceson
mesh_terms: D015550:Cell Degranulation; D003602:Cytotoxicity, Immunologic; D005260:Female; D016368:Frameshift Mutation; D006720:Homozygote; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology / Q000502:physiology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000235:genetics; D050765:Qa-SNARE Proteins / Q000235:genetics*
chemical_list: D050765:Qa-SNARE Proteins