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Unusual functional manifestations of a novel STX11 frameshift mutation in two infants with familial hemophagocytic lymphohistiocytosis type 4 (FHL4)
Author(s) -
Macartney Christine A.,
Weitzman Sheila,
Wood Stephanie M.,
Bansal Deepak,
Steele MacGregor,
Meeths Marie,
Abdelhaleem Mohamed,
Bryceson Yenan T.
Publication year - 2011
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.22676
Subject(s) - frameshift mutation , hemophagocytic lymphohistiocytosis , degranulation , medicine , immunology , immune system , mutation , cytotoxicity , genetics , disease , gene , biology , in vitro , receptor
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. Pediatr Blood Cancer 2011;56:654–657. © 2010 Wiley‐Liss, Inc.