RESUMO
INTRODUCTION AND OBJECTIVES: Pediatric Systemic Lupus Erythematosus (pSLE) is an autoimmune disorder of children. Early disease onset raises the probability of genetic etiology and it is more severe than adult SLE. PATIENTS AND METHODS: Herein an eight-year-old girl with pSLE from consanguineous parents is reported. RESULTS: Although she was diagnosed as pSLE since the age of two years, Whole Exome Sequencing (WES) revealed a rare stop-gained C>T mutation in C1QA gene. The variant was validated and segregated in patient and the family. Furthermore, serum levels of the C1q protein were measured and found to be much lower than normal ranges. CONCLUSIONS: This study indicated that C1Q deficiency should be considered as a differential diagnosis of pSLE. Therefore, measurement of C1q should be recommended in all cases with pSLE
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Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Complemento C1q , Genótipo , Lúpus Eritematoso Sistêmico/genética , Deleção de Sequência/genética , Consanguinidade , Homozigoto , Exoma/genéticaRESUMO
INTRODUCTION AND OBJECTIVES: Pediatric Systemic Lupus Erythematosus (pSLE) is an autoimmune disorder of children. Early disease onset raises the probability of genetic etiology and it is more severe than adult SLE. PATIENTS AND METHODS: Herein an eight-year-old girl with pSLE from consanguineous parents is reported. RESULTS: Although she was diagnosed as pSLE since the age of two years, Whole Exome Sequencing (WES) revealed a rare stop-gained C>T mutation in C1QA gene. The variant was validated and segregated in patient and the family. Furthermore, serum levels of the C1q protein were measured and found to be much lower than normal ranges. CONCLUSIONS: This study indicated that C1Q deficiency should be considered as a differential diagnosis of pSLE. Therefore, measurement of C1q should be recommended in all cases with pSLE.
Assuntos
Complemento C1q/genética , Genótipo , Lúpus Eritematoso Sistêmico/genética , Deleção de Sequência/genética , Criança , Pré-Escolar , Consanguinidade , Feminino , Homozigoto , Humanos , Linhagem , Sequenciamento do ExomaRESUMO
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.
