RESUMEN
The second affiliation of the corresponding author Eda Tahir Turanli was incorrectly published as Istanbul Medeniyet University instead of Istanbul Technical University.
RESUMEN
Systemic autoinflammatory diseases (sAIDs) are a heterogeneous group of disorders, having monogenic inherited forms with overlapping clinical manifestations. More than half of patients do not carry any pathogenic variant in formerly associated disease genes. Here, we report a cross-sectional study on targeted Next-Generation Sequencing (NGS) screening in patients with suspected sAIDs to determine the diagnostic utility of genetic screening. Fifteen autoinflammation/immune-related genes (ADA2-CARD14-IL10RA-LPIN2-MEFV-MVK-NLRC4-NLRP12-NLRP3-NOD2-PLCG2-PSTPIP1-SLC29A3-TMEM173-TNFRSF1A) were used to screen 196 subjects from adult/pediatric clinics, each with an initial clinical suspicion of one or more sAID diagnosis with the exclusion of typical familial Mediterranean fever (FMF) patients. Following the genetic screening, 140 patients (71.4%) were clinically followed-up and re-evaluated. Fifty rare variants in 41 patients (20.9%) were classified as pathogenic or likely pathogenic and 32 of those variants were located on the MEFV gene. We detected pathogenic or likely pathogenic variants compatible with the final diagnoses and inheritance patterns in 14/140 (10%) of patients for the following sAIDs: familial Mediterranean fever (n = 7), deficiency of adenosine deaminase 2 (n = 2), mevalonate kinase deficiency (n = 2), Muckle-Wells syndrome (n = 1), Majeed syndrome (n = 1), and STING-associated vasculopathy with onset in infancy (n = 1). Targeted NGS panels have impact on diagnosing rare monogenic sAIDs for a group of patients. We suggest that MEFV gene screening should be first-tier genetic testing especially in regions with high carrier rates. Clinical utility of multi-gene testing in sAIDs was as low as expected, but extensive genome-wide familial analyses in combination with exome screening would enlighten additional genetic factors causing disease.
Asunto(s)
Pruebas Genéticas , Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Secuenciación de Nucleótidos de Alto Rendimiento , Proteínas Adaptadoras Transductoras de Señales/genética , Adenosina Desaminasa/deficiencia , Adenosina Desaminasa/genética , Adolescente , Adulto , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/genética , Anemia Diseritropoyética Congénita/diagnóstico , Anemia Diseritropoyética Congénita/genética , Proteínas Adaptadoras de Señalización CARD/genética , Proteínas de Unión al Calcio/genética , Niño , Preescolar , Síndromes Periódicos Asociados a Criopirina/diagnóstico , Síndromes Periódicos Asociados a Criopirina/genética , Proteínas del Citoesqueleto/genética , Fiebre Mediterránea Familiar/diagnóstico , Fiebre Mediterránea Familiar/genética , Femenino , Enfermedades Autoinflamatorias Hereditarias/genética , Humanos , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Masculino , Deficiencia de Mevalonato Quinasa/diagnóstico , Deficiencia de Mevalonato Quinasa/genética , Persona de Mediana Edad , Proteínas de Transporte de Nucleósidos/genética , Osteomielitis/diagnóstico , Osteomielitis/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Pirina/genética , Análisis de Secuencia de ADN , Inmunodeficiencia Combinada Grave/diagnóstico , Inmunodeficiencia Combinada Grave/genética , Adulto JovenRESUMEN
Pediatric rheumatology includes autoinflammatory monogenic diseases, autoinflammatory multifactorial diseases with complex inheritance, and diseases with uncertain clinical diagnosis or undefined conditions, even though they show signs of autoinflammation. Most of these diseases are systemic; it is important to diagnose patients promptly and definitively and to select proper treatment options based on the diagnoses. Clinical observation and acute-phase responses are usually sufficient for diagnosis; however, genetic analyses can provide supportive data for definite diagnosis and treatment, especially for rare monogenic diseases. As for multifactorial autoinflammatory diseases, susceptibility genes, and factors involved in the etiopathogenesis have not been fully identified. It is possible to identify disease genes and novel diseases, and lead to new treatment options by gene mapping studies and high-throughput screening strategies for multifactorial diseases and conditions with uncertain clinical characteristics. In this review, we discuss the three groups of autoinflammatory diseases and role of genetics in their diagnosis.