Human DOCK2 Deficiency: Report of a Novel Mutation and Evidence for Neutrophil Dysfunction.
J Clin Immunol
; 39(3): 298-308, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-30838481
DOCK2 is a guanine-nucleotide-exchange factor for Rac proteins. Activated Rac serves various cellular functions including the reorganization of the actin cytoskeleton in lymphocytes and neutrophils and production of reactive oxygen species in neutrophils. Since 2015, six unrelated patients with combined immunodeficiency and early-onset severe viral infections caused by bi-allelic loss-of-function mutations in DOCK2 have been described. Until now, the function of phagocytes, specifically neutrophils, has not been assessed in human DOCK2 deficiency. Here, we describe a new kindred with four affected siblings harboring a homozygous splice-site mutation (c.2704-2 A > C) in DOCK2. The mutation results in alternative splicing and a complete loss of DOCK2 protein expression. The patients presented with leaky severe combined immunodeficiency or Omenn syndrome. The novel mutation affects EBV-B cell migration and results in NK cell dysfunction similar to previous observations. Moreover, both cytoskeletal rearrangement and reactive oxygen species production are partially impaired in DOCK2-deficient neutrophils.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Células Matadoras Naturais
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Imunodeficiência Combinada Severa
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Deleção de Sequência
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Proteínas Ativadoras de GTPase
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Fatores de Troca do Nucleotídeo Guanina
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Neutrófilos
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article