RESUMEN
Hereditary Angioedema is an autosomal dominant inherited disease leading to oedema attacks with variable severity and localization predominantly caused by C1-INH deficit. More than 400 mutations have been already identified, however no genetic analysis of a Brazilian cohort of HAE patients with C1-INH deficiency has been published. Our aim was to perform genetic analysis of C1-INH gene (SERPING1) in Brazilian HAE patients. We screened the whole SERPING1 coding region from 30 subjects out of 16 unrelated families with confirmed diagnosis of HAE due to C1-INH deficiency. Clinical diagnosis was based on symptoms and quantitative and/or functional analysis of C1-INH. We identified fifteen different mutations among which eight were not previously described according to databases. We found five small deletions (c.97_115del19; c.553delG; c.776_782del7; c.1075_1089del15 and c.1353_1354delGA), producing frameshifts leading to premature stop codons; seven missense mutations (c.498C>A; c.550G>C; c.752T>C; c.889G>A; c.1376C>A; c.1396C>T; c.1431C>A); one nonsense mutation (c.1480C>T), and two intronic alterations (c.51+1G>T; c.51+2T>C). Despite the small number of participants in this study, our results show mutations not previously identified in SERPING1 gene. This study represents the first Brazilian HAE cohort evaluated for mutations and it introduces the possibility to perform genetic analysis in case of need for differential diagnosis.
Asunto(s)
Angioedemas Hereditarios/genética , Proteínas Inactivadoras del Complemento 1/genética , Mutación , Adolescente , Adulto , Anciano , Angioedemas Hereditarios/sangre , Angioedemas Hereditarios/diagnóstico , Brasil , Niño , Proteína Inhibidora del Complemento C1 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
AIM: We analyzed data from 71 patients with chronic granulomatous disease (CGD) with a confirmed genetic diagnosis, registered in the online Latin American Society of Primary Immunodeficiencies (LASID) database. RESULTS: Latin American CGD patients presented with recurrent and severe infections caused by several organisms. The mean age at disease onset was 23.9 months, and the mean age at CGD diagnosis was 52.7 months. Recurrent pneumonia was the most frequent clinical condition (76.8%), followed by lymphadenopathy (59.4%), granulomata (49.3%), skin infections (42%), chronic diarrhea (41.9%), otitis (29%), sepsis (23.2%), abscesses (21.7%), recurrent urinary tract infection (20.3%), and osteomyelitis (15.9%). Adverse reactions to bacillus Calmette-Guérin (BCG) vaccination were identified in 30% of the studied Latin American CGD cases. The genetic diagnoses of the 71 patients revealed 53 patients from 47 families with heterogeneous mutations in the CYBB gene (five novel mutations: p.W361G, p.C282X, p.W483R, p.R226X, and p.Q93X), 16 patients with the common deletion c.75_76 del.GT in exon 2 of NCF1 gene, and two patients with mutations in the CYBA gene. CONCLUSION: The majority of Latin American CGD patients carry a hemizygous mutation in the CYBB gene. They also presented a wide range of clinical manifestations most frequently bacterial and fungal infections of the respiratory tract, skin, and lymph nodes. Thirty percent of the Latin American CGD patients presented adverse reactions to BCG, indicating that this vaccine should be avoided in these patients.
Asunto(s)
Enfermedad Granulomatosa Crónica , Glicoproteínas de Membrana/genética , Mutación , NADPH Oxidasas/genética , Sistema de Registros , Absceso/epidemiología , Absceso/etiología , Absceso/genética , Adolescente , Edad de Inicio , Niño , Preescolar , Diarrea/epidemiología , Diarrea/etiología , Diarrea/genética , Femenino , Enfermedad Granulomatosa Crónica/complicaciones , Enfermedad Granulomatosa Crónica/epidemiología , Enfermedad Granulomatosa Crónica/genética , Hispánicos o Latinos , Humanos , Lactante , Recién Nacido , Enfermedades Linfáticas/epidemiología , Enfermedades Linfáticas/etiología , Enfermedades Linfáticas/genética , Masculino , NADPH Oxidasa 2 , Osteomielitis/epidemiología , Osteomielitis/etiología , Osteomielitis/genética , Otitis/epidemiología , Otitis/etiología , Otitis/genética , Neumonía/epidemiología , Neumonía/etiología , Neumonía/genética , Sepsis/epidemiología , Sepsis/etiología , Sepsis/genética , Enfermedades de la Piel/epidemiología , Enfermedades de la Piel/etiología , Enfermedades de la Piel/genética , Infecciones Urinarias/epidemiología , Infecciones Urinarias/etiología , Infecciones Urinarias/genéticaRESUMEN
Objetivo: Analisar aspectos clínicos de pacientes com infecções graves e/ u de repetição sugestivas de distúrbio fagocitário encaminhado s a um laboratório especializado para avaliação do sistema APDH oxidase. Métodos: Foram estudados 53 pacientes com suspeita de defeito no sistema ADPH oxidase. Avaliação laboratorial constou de teste do NBT e dosagem de ânion superóxido liberado por neutrófilos e células mononucleares. Os pacientes foram classificados em grupo I com Doença Granulomatosa. Crônica (DGC) e grupo II sem doença determinada. Resulta os: O grupo I foi composto por 20 pacientes e grupo II por 33 pacientes. As infecções pulmonares foram as mais freqüentes nos dois grupos, seguidas de adenites, infecções cutâneas e abscessos profundos no grupo I e otite média, infecção de pele e amigdalite no grupo II. Observou-se diferença estatisticamente significativa para infecção urinária (p=0,0097), abscessos profundos (p=0,0012) e linfadenopatias (p=0,0003). Reação adversas à vacina BCG foi observada em cinco pacientes do grupo I e apenas um paciente do grupo II (p=0,0240). A história familiar de infecção de repetição foi referida por doze pacientes do grupo I e por 8 pacientes do grupo II (p=0,0181). Conclusão: A presença de história familiar de infecção de repetição, reação à vacina BCG, linfadenites e abscessos profundos apresentaram associação a grupo com diagnóstico bioquímico de DGC. Infecção urinária teve associada ao grupo sem diagnóstico definido, mas com suspeita clínica de defeito de fagócito.