Assuntos
Síndromes de Imunodeficiência/genética , Quinases Associadas a Receptores de Interleucina-1/genética , Linfoma não Hodgkin/genética , Mutação/genética , Infecções por Salmonella/genética , Adolescente , Feminino , Humanos , Lactente , Masculino , Doenças da Imunodeficiência Primária , IrmãosRESUMO
No disponible
Assuntos
Humanos , Masculino , Feminino , Lactente , Adolescente , Receptores de Interleucina-1/deficiência , Mutação/genética , Homozigoto , Recidiva , Meningites Bacterianas/genética , Infecções por Salmonella/genética , Fator 88 de Diferenciação Mieloide/deficiênciaRESUMO
Primary immunodeficiencies (PIDs) represent a large group of disorders with an increased susceptibility to infections. Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiencies (PIDs) with marked T-cell lymphopenia. Investigation of the genetic aetiology using classical Sanger sequencing is associated with considerable diagnostic delay. We here established a custom-designed, next-generation sequencing (NGS)-based panel to efficiently identify disease-causing genetic defects in PID patients and applied this method in SCID patients of Turkish origin with previously undefined genetic aetiology. We used HaloPlex enrichment technology, a targeted, NGS-based method which was designed to diagnose patients with SCID and other PIDs. Our HaloPlex panel included a total of 356 PID-related genes, and we searched disease-causing mutations in 19 Turkish SCID patients without a genetic diagnosis. The coverage of targeted regions ranged from 97.47% to 99.62% with an average of 98.31% for all patients. All known SCID genes were covered with a percentage of at least 97.3%. We made a genetic diagnosis in six of 19 (33%) patients, including four novel disease-causing mutations identified in RAG1, JAK3 and IL2RG, respectively. We showed that this NGS-based method can provide rapid genetic diagnosis for patients suffering from SCID, potentially facilitating clinical treatment decisions.
Assuntos
Predisposição Genética para Doença , Imunodeficiência Combinada Severa/genética , Sequência de Bases , Citidina Desaminase/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas de Homeodomínio/genética , Humanos , Lactente , Subunidade gama Comum de Receptores de Interleucina/genética , Subunidade alfa de Receptor de Interleucina-10/genética , Subunidade beta de Receptor de Interleucina-10/genética , Janus Quinase 3/genética , Masculino , Análise de Sequência de DNA , Telomerase/genética , TurquiaRESUMO
Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder caused by inherited defects in the nicotinamide adenine dinucleotide phosphate oxidase complex. The neutrophils of patient with CGD can ingest bacteria normally, but the oxidative processes that lead to superoxide anion formation, hydrogen peroxide production, nonoxidative pathway activation, and bacterial killing are impaired. Serious infections result from microorganisms that produce catalase. Immunoglobulin levels of patients with CGD are usually normal or elevated. We describe a patient with CGD associated with hypogammaglobulinemia, an unusual co-occurrence.
