NCKAP1L defects lead to primary immunodeficincy and lymphoproliferation within a Hemophagocytic Lymphohistiocytosis-like syndrome

The Nck-Associated Protein 1-Like NCKAP1L gene, alternatively called Hematopoietic protein 1 (HEM-1), encodes a hematopoietic-specific regulator of the actin cytoskeleton, part of the WAVE2 complex. NCKAP1L is involved in lymphocyte development, phagocytosis and neutrophils migration. Here we report the first cases of NCKAP1L-deficiency in man, as homozygous non-sense or splice variants, observed in 2 independent patients of Middle-Eastern origin of 1.5 months and 9 years of age respectively. We described a novel nosological entity, combining to various degrees, immune deficiency, lymphoproliferation within a highly inflammatory syndrome, reminiscent, yet distinct of HLH; due to recessive mutations in NCKAP1L.