A RAB27A 5′ untranslated region structural variant associated with late-onset hemophagocytic lymphohistiocytosis and normal pigmentation

Autosomal-recessive mutations in genes required for secretory lysosome-mediated lymphocyte cytotoxicity cause primary hemophagocytic lymphohistiocytosis (HLH), an early-onset, life-threatening hyperinflammatory syndrome.1 Similarly, mutations in RAB27A and LYST are associated with HLH, yet manifest hypopigmentation, because Rab27a and LYST also facilitate trafficking of pigment-containing lysosomes in melanocytes.2 We detail individuals from 5 families from the Baltic area with a novel structural variant at the 5′ untranslated region (UTR) of RAB27A associated with an atypical form of Griscelli syndrome type 2 (GS2) manifesting as late-onset HLH, marked neuroinflammation, skin granulomas, lymphoma, and normal pigmentation (see Table E1 in this article's Online Repository at www.jacionline.org).