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

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood

SUBMITTER: Aurélie Hirschler

LAB HEAD: Carapito Christine

PROVIDER: PXD018042 | Pride | 2020-07-23

REPOSITORIES: Pride

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			Action	DRS
	Humannew_pSP_AUH_20190715.fasta	Fasta
	QE30771AUH.raw	Raw
	QE30773AUH.raw	Raw
	QE30775AUH.raw	Raw
	QE30777AUH.raw	Raw

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

Project description: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.

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RNAseq on PBMC of two patients with a novel syndromic entity combining immunodeficiency, lymphoproliferation and HLH-like phenotypes, and three age and sex-matched controls for each patient.

Project description:The study describes two independent cases of NCKAP1L-deficiency, both carrying homozygous non-sense or splice variants in the NCKAP1L gene. The patients presented a phenotype of immunodeficiency, lymphoproliferation and hyperinflammation with features of Hemophagocytic Lymphohistiocytosis (HLH).

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