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1.
Pediatr Blood Cancer ; 63(9): 1653-6, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27163649

RESUMO

Humoral and cellular immunity were studied in 28 children completing conventional treatment of standard-risk (SR) or intermediate-risk (IR) acute lymphoblastic leukemia (ALL). Both naïve and memory B cells were most severely affected and showed slow recovery during the 2-year follow-up, while the T-cell compartment showed only minor changes. Immunoglobulins and IgG subclasses, components, and antibodies against vaccine-preventable diseases were not significantly affected. In conclusion, immune recovery after conventional chemotherapy for SR and IR ALL is marked by B-cell depletion, but otherwise did not show any severe deficiencies in lymphocyte function.


Assuntos
Linfócitos B/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Via Alternativa do Complemento , Humanos , Imunidade Humoral , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia
2.
Pediatr Infect Dis J ; 35(2): 123-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26440814

RESUMO

BACKGROUND: The incidence of invasive group A streptococcus (iGAS) infections varies in time and geographically for unknown reasons. We performed a nationwide survey to assess the population-based incidence rates and outcomes of children with iGAS infections. METHODS: We collected data on patients from hospital discharge registries and the electronic databases of microbiological laboratories in Finland for the period 1996-2010. We then recorded the emm types or serotypes of the strains. The study physician visited all university clinics and collected the clinical data using the same data entry sheet. RESULTS: We identified 151 children with iGAS infection. Varicella preceded iGAS infection in 20% of cases and fasciitis infection in 83% of cases. The annual incidence rate of iGAS infection was 0.93 per 100,000 in 1996-2000, 1.80 in 2001-2005 and 2.50 in 2006-2010. The proportion of emm 1.0 or T1M1 strains peaked in 1996-2000 and again in 2006-2010, to 44% and 37% of all typed isolates. The main clinical diagnoses of the patients were severe soft-tissue infection (46%), sepsis (28%), empyema (10%), osteoarticular infection (9%) and primary peritonitis (5%). Severe pain was the most typical symptom for soft-tissue infections. More than half of the patients underwent surgery and received clindamycin. The readmission rate was 7%, and the case fatality rate was 2%. CONCLUSIONS: The incidence rate of pediatric iGAS infections tripled during our study. The increase was not, however, the result of a change in the strain types causing iGAS. Varicella immunization would likely have prevented a significant number of the cases.


Assuntos
Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/patologia , Streptococcus pyogenes/isolamento & purificação , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Técnicas de Tipagem Bacteriana , Proteínas de Transporte/genética , Criança , Pré-Escolar , Feminino , Finlândia/epidemiologia , Genótipo , Humanos , Incidência , Masculino , Sorogrupo , Sorotipagem , Infecções Estreptocócicas/microbiologia , Resultado do Tratamento
3.
Duodecim ; 131(6): 541-4, 2015.
Artigo em Finlandês | MEDLINE | ID: mdl-26237897

RESUMO

The DOCK8 hyperimmunoglobulin E syndrome is an autosomal recessive primary combined immunological deficiency. Severe atopic eczema having its onset in infancy, food allergies, chronic viral infections of the skin, and recurrent pneumonias are central symptoms. Serum IgE level is high and eosinophilia is found in the blood. In addition, abnormalities in the number and function of lymphocytes can be detected. The disease may be difficult to distinguish from severe allergic eczema and asthma. The diagnosis is made through a gene test. We describe a 13-year-old boy, whose disease was cured with allogenic stem cell transplantation.


Assuntos
Fatores de Troca do Nucleotídeo Guanina/genética , Síndrome de Job/genética , Síndrome de Job/terapia , Transplante de Células-Tronco , Adolescente , Asma/diagnóstico , Eczema/diagnóstico , Fatores de Troca do Nucleotídeo Guanina/imunologia , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Síndrome de Job/diagnóstico , Síndrome de Job/imunologia , Masculino
4.
J Clin Immunol ; 35(2): 189-98, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25627830

RESUMO

Mutations in DOCK8 result in autosomal recessive Hyper-IgE syndrome with combined immunodeficiency (CID). However, the natural course of disease, long-term prognosis, and optimal therapeutic management have not yet been clearly defined. In an international retrospective survey of patients with DOCK8 mutations, focused on clinical presentation and therapeutic measures, a total of 136 patients with a median follow-up of 11.3 years (1.3-47.7) spanning 1693 patient years, were enrolled. Eczema, recurrent respiratory tract infections, allergies, abscesses, viral infections and mucocutaneous candidiasis were the most frequent clinical manifestations. Overall survival probability in this cohort [censored for hematopoietic stem cell transplantation (HSCT)] was 87 % at 10, 47 % at 20, and 33 % at 30 years of age, respectively. Event free survival was 44, 18 and 4 % at the same time points if events were defined as death, life-threatening infections, malignancy or cerebral complications such as CNS vasculitis or stroke. Malignancy was diagnosed in 23/136 (17 %) patients (11 hematological and 9 epithelial cancers, 5 other malignancies) at a median age of 12 years. Eight of these patients died from cancer. Severe, life-threatening infections were observed in 79/136 (58 %); severe non-infectious cerebral events occurred in 14/136 (10 %). Therapeutic measures included antiviral and antibacterial prophylaxis, immunoglobulin replacement and HSCT. This study provides a comprehensive evaluation of the clinical phenotype of DOCK8 deficiency in the largest cohort reported so far and demonstrates the severity of the disease with relatively poor prognosis. Early HSCT should be strongly considered as a potential curative measure.


Assuntos
Estudos de Associação Genética , Fatores de Troca do Nucleotídeo Guanina/deficiência , Fatores de Troca do Nucleotídeo Guanina/genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Incidência , Lactente , /epidemiologia , Síndrome de Job/complicações , Síndrome de Job/diagnóstico , Síndrome de Job/genética , Síndrome de Job/imunologia , Síndrome de Job/mortalidade , Síndrome de Job/terapia , Contagem de Linfócitos , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias/epidemiologia , Neoplasias/etiologia , Fenótipo , Adulto Jovem
5.
Blood ; 125(4): 639-48, 2015 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-25349174

RESUMO

The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of immunodysregulation polyendocrinopathy enteropathy X-linked-like syndrome. Here, we immunologically characterized 3 patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T, and p.K658N, respectively). The patients displayed multiorgan autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B-cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4(-)CD8(-)) T cells, and decreased natural killer, T helper 17, and regulatory T-cell numbers. Notably, the patient harboring the K392R mutation developed T-cell large granular lymphocytic leukemia at age 14 years. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.


Assuntos
Agamaglobulinemia , Doenças Autoimunes , Doenças Genéticas Inatas , Leucemia Linfocítica Granular Grande , Mutação de Sentido Incorreto , Infecções por Mycobacterium , Fator de Transcrição STAT3 , Adolescente , Adulto , Agamaglobulinemia/genética , Agamaglobulinemia/imunologia , Agamaglobulinemia/patologia , Substituição de Aminoácidos , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Linfócitos B/imunologia , Linfócitos B/patologia , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Células Dendríticas/imunologia , Células Dendríticas/patologia , Feminino , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/imunologia , Doenças Genéticas Inatas/patologia , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Leucemia Linfocítica Granular Grande/genética , Leucemia Linfocítica Granular Grande/imunologia , Leucemia Linfocítica Granular Grande/patologia , Infecções por Mycobacterium/genética , Infecções por Mycobacterium/imunologia , Infecções por Mycobacterium/patologia , Estrutura Terciária de Proteína , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Células Th17/imunologia , Células Th17/patologia
6.
Antioxid Redox Signal ; 21(16): 2231-45, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24787605

RESUMO

AIMS: Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations in the phagocyte reactive oxygen species (ROS)-producing NOX2 enzyme complex and characterized by recurrent infections associated with hyperinflammatory and autoimmune manifestations. A translational, comparative analysis of CGD patients and the corresponding ROS-deficient Ncf1(m1J) mutated mouse model was performed to reveal the molecular pathways operating in NOX2 complex deficient inflammation. RESULTS: A prominent type I interferon (IFN) response signature that was accompanied by elevated autoantibody levels was identified in both mice and humans lacking functional NOX2 complex. To further underline the systemic lupus erythematosus (SLE)-related autoimmune process, we show that naïve Ncf1(m1J) mutated mice, similar to SLE patients, suffer from inflammatory kidney disease with IgG and C3 deposits in the glomeruli. Expression analysis of germ-free Ncf1(m1J) mutated mice reproduced the type I IFN signature, enabling us to conclude that the upregulated signaling pathway is of endogenous origin. INNOVATION: Our findings link the previously unexplained connection between ROS deficiency and increased susceptibility to autoimmunity by the discovery that activation of IFN signaling is a major pathway downstream of a deficient NOX2 complex in both mice and humans. CONCLUSION: We conclude that the lack of phagocyte-derived oxidative burst is associated with spontaneous autoimmunity and linked with type I IFN signature in both mice and humans.


Assuntos
Doença Granulomatosa Crônica/genética , Imunoglobulina G/imunologia , Interferon-alfa/genética , Interferon beta/genética , NADPH Oxidases/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/imunologia , Adolescente , Adulto , Animais , Autoimunidade/imunologia , Criança , Pré-Escolar , Complemento C3/imunologia , Modelos Animais de Doenças , Feminino , Expressão Gênica , Doença Granulomatosa Crônica/imunologia , Humanos , Interferon-alfa/imunologia , Interferon beta/imunologia , Glomérulos Renais/imunologia , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/imunologia , Camundongos , NADPH Oxidase 2 , NADPH Oxidases/imunologia , Adulto Jovem
8.
J Clin Immunol ; 34(2): 256-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24402619

RESUMO

PURPOSE: To study the changes in the immunological status in 2 children with cartilage hair hypoplasia (CHH). METHODS: A 4-6 year immunological follow-up from infancy. RESULTS: In infancy the children presented a combined T cell and B cell immunodeficiency which partly resolved in time. Mitogen-induced T cell proliferation values fluctuated but lymphopenia has remained constant. Both patients had no recent thymic emigrants (TREC). Both children have suffered from a prolonged viral infection. Hypogammaglobulinemia normalized during the first years of life but both children have a specific antibody deficiency (SAD). CONCLUSIONS: The changes in the immunological status in CHH patients emphasize the importance of a regular follow-up. SAD should be searched for in CHH. The absence of TRECs supports combined immunodeficiency and possible need of hematopoietic stem cell transplantation.


Assuntos
Cabelo/anormalidades , Doença de Hirschsprung/imunologia , Síndromes de Imunodeficiência/imunologia , Osteocondrodisplasias/congênito , Feminino , Seguimentos , Genótipo , Cabelo/imunologia , Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/genética , Doença de Hirschsprung/terapia , Humanos , Imunidade Celular/genética , Imunidade Celular/imunologia , Imunidade Humoral/genética , Imunidade Humoral/imunologia , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/terapia , Lactente , Recém-Nascido , Ativação Linfocitária/imunologia , Masculino , Mutação , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/genética , Osteocondrodisplasias/imunologia , Osteocondrodisplasias/terapia
9.
Hum Immunol ; 73(5): 498-501, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22406254

RESUMO

Increased susceptibility to recurrent viral and bacterial respiratory infections in children and young adults is not well understood. To evaluate the role of complement factor C4 in the defense against respiratory infections, we studied complement factor C4 allotypes C4A and C4B and copy numbers of C4A and C4B genes in 84 children and young adults with recurrent acute otitis media, sinusitis, or pneumonia and in 74 healthy controls. The occurrence of C4A gene deficiency was significantly higher in patients compared with controls (26% vs 14%, p = 0.048). Girls predominated in the group of patients with C4A deficiency (73% girls and 27% boys, p = 0.004). The lectin pathway of complement was more often functionally impaired in patients with C4A deficiency than in patients with no C4A deficiency (41% vs 13%, p = 0.033). Classical and alternative pathways were normal in individuals with C4 null alleles. C4A deficiency is 1 of the minor defects of the innate immunity that may predispose children and young adults to recurrent respiratory infections. C4 gene testing should be added to the list of investigations when the cause for recurrent acute otitis media, maxillary sinusitis, or pneumonia in children and young adults is sought.


Assuntos
Complemento C4a/imunologia , Imunidade Inata/genética , Otite Média/genética , Pneumonia/genética , Sinusite/genética , Doença Aguda , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Complemento C4a/deficiência , Complemento C4a/genética , Complemento C4b/genética , Complemento C4b/imunologia , Lectina de Ligação a Manose da Via do Complemento/imunologia , Feminino , Dosagem de Genes/imunologia , Frequência do Gene , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Otite Média/imunologia , Pneumonia/imunologia , Recidiva , Fatores Sexuais , Sinusite/imunologia
10.
J Allergy Clin Immunol ; 126(1): 120-6, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20541246

RESUMO

BACKGROUND: The occurrence of respiratory tract viral infections in patients with primary hypogammaglobulinemia has not been studied. OBJECTIVE: We conducted a prospective 12-month follow-up study of respiratory tract infections in 12 adult patients with primary hypogammaglobulinemia. METHODS: Nasal swab samples and induced sputum samples were taken at the onset of acute respiratory tract infection and every 3 months thereafter. Samples were tested for bacteria and viruses. PCR tests were performed for 15 respiratory tract viruses. In case the results for rhinovirus were positive, follow-up nasal swab samples were taken every 2 weeks until rhinoviral PCR results became negative. Patients completed symptom diaries, which were collected every month. The spouses of the patients served as healthy control subjects. RESULTS: During the 12-month period, the 12 patients had 65 episodes of acute respiratory tract infections, and the 11 spouses had 12 acute episodes (P < .001). Respiratory tract viruses were found in sputum in 54% of the infections. Rhinovirus was the most common virus. In more than half of our patients, rhinoviral PCR results stayed positive for more than 2 months. The most long-acting persistence with the same rhinovirus was 4 months. CONCLUSIONS: Despite adequate immunoglobulin replacement therapy, patients with primary hypogammaglobulinemia have increased susceptibility to respiratory tract viral infections. Rhinoviral infections are frequent and prolonged.


Assuntos
Agamaglobulinemia/complicações , Infecções Respiratórias/epidemiologia , Viroses/epidemiologia , Adulto , Agamaglobulinemia/virologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Infecções Respiratórias/etiologia , Rhinovirus/isolamento & purificação , Escarro/microbiologia , Escarro/virologia
12.
J Clin Microbiol ; 46(12): 4104-5, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18842946

RESUMO

Human bocavirus (HBoV) is one of the recently identified respiratory viruses. The clinical features of HBoV infection have not yet been fully elucidated. We report an invasive HBoV infection and hepatitis in a boy with cartilage-hair hypoplasia and severe T-cell immunodeficiency.


Assuntos
Bocavirus/isolamento & purificação , Hepatite Viral Humana/diagnóstico , Síndromes de Imunodeficiência/complicações , Infecções por Parvoviridae/diagnóstico , Hepatite Viral Humana/virologia , Humanos , Lactente , Masculino , Infecções por Parvoviridae/virologia
13.
Arch Otolaryngol Head Neck Surg ; 133(6): 597-602, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17576911

RESUMO

OBJECTIVE: To study bacteria and viruses in maxillary sinuses of patients with primary hypogammaglobulinemia receiving immunoglobulin therapy. DESIGN: Prospective cross-sectional study during 6 months. SETTING: Tertiary care university hospital. PATIENTS: Seventeen patients with primary hypogammaglobulinemia (10 males and 7 females; mean age, 39 years [age range, 11-71 years]). Sixteen patients had common variable immunodeficiency, and 1 patient had X-linked agammaglobulinemia. MAIN OUTCOME MEASURES: Magnetic resonance imaging and x-ray imaging of paranasal sinuses when patients did not have signs of acute infection and reevaluation 6 months later. Maxillary sinus aspiration and lavage were performed at a follow-up visit. Sinus fluid analysis for bacteria and viruses was performed by culture and by polymerase chain reaction. A questionnaire on symptoms related to sinusitis was administered during the follow-up period. RESULTS: Among 17 patients, 9 (53%) had radiologically defined sinusitis without subjective symptoms at study enrollment. At reevaluation 6 months later, radiological findings remained unchanged in two thirds of the patients. Among 15 patients, bacteria were found in sinus lavage samples from 13 patients, and viruses were found in samples from 7 patients. Eight patients had 2 pathogens or more on bacterial culture. Rhinovirus was identified from sinus lavage samples in 5 patients (33%), enterovirus in 3 patients (20%), and respiratory syncytial virus in 1 patient (7%). Pathogenic bacteria were found in maxillary sinuses of all patients who tested positive for rhinovirus and enterovirus. No fungi were found. During the follow-up period, 6 patients reported mucopurulent drainage. CONCLUSIONS: Bacteria and viruses were commonly found in maxillary sinuses of patients with primary hypogammaglobulinemia. Yearly evaluation by an ear, nose, and throat surgeon is recommended.


Assuntos
Agamaglobulinemia/microbiologia , Bactérias/classificação , Seio Maxilar/microbiologia , Vírus/classificação , Adolescente , Adulto , Agamaglobulinemia/virologia , Idoso , Criança , Imunodeficiência de Variável Comum/microbiologia , Imunodeficiência de Variável Comum/virologia , Estudos Transversais , Enterovirus/isolamento & purificação , Feminino , Seguimentos , Doenças Genéticas Ligadas ao Cromossomo X/microbiologia , Doenças Genéticas Ligadas ao Cromossomo X/virologia , Haemophilus influenzae/isolamento & purificação , Humanos , Imagem por Ressonância Magnética , Masculino , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/virologia , Sinusite Maxilar/microbiologia , Sinusite Maxilar/virologia , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Rhinovirus/isolamento & purificação
15.
J Infect Dis ; 190(8): 1369-73, 2004 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-15378427

RESUMO

BACKGROUND: Influenza vaccination of healthy children is encouraged because children are frequently hospitalized for influenza-attributable illnesses. However, most children with influenza are treated as outpatients, and scarce data are available on the burden of influenza in these children. METHODS: We performed a prospective study of respiratory infections in preenrolled cohorts of children < or = 13 years old during 2 consecutive respiratory seasons (2231 child-seasons of follow-up). At any sign of respiratory infection, we examined the children and obtained a nasal swab for the detection of influenza. The parents filled out daily symptom diaries. Of all the enrollees, 94% remained active participants in the study. RESULTS: The average annual rate of influenza was highest (179 cases/1000 children) among children < 3 years old. Acute otitis media developed as a complication of influenza in 39.7% of children < 3 years old. For every 100 influenza-infected children < 3 years old, there were 195 days of parental work loss (mean duration, 3.2 days). CONCLUSIONS: Influenza causes a substantial burden of illness on outpatient children and their families. Vaccination of children < 3 years old might be beneficial for reducing the direct and indirect costs of influenza in children.


Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Influenza Humana/epidemiologia , Infecções Respiratórias/epidemiologia , Doença Aguda , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Infecções Comunitárias Adquiridas/economia , Efeitos Psicossociais da Doença , Feminino , Finlândia/epidemiologia , Humanos , Lactente , Influenza Humana/economia , Masculino , Otite Média/economia , Otite Média/epidemiologia , Estudos Prospectivos , Infecções Respiratórias/economia
16.
Pediatr Infect Dis J ; 22(10 Suppl): S204-6, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14551475

RESUMO

BACKGROUND: Influenza is an important cause of respiratory illness in children, but data on virologically confirmed influenza infections in children treated as outpatients are limited. METHODS: We carried out a prospective cohort study of normal children younger than 13 years (n = 1338) in the winter of 2000 to 2001. During the study period of 32 weeks, the children were examined at the study clinic whenever they had fever or signs of respiratory infection. Nasal swabs were obtained during each episode of infection for determination of the viral etiology of the illness. RESULTS: The overall attack rate of influenza in the cohort was 18.8%. Influenza viruses were isolated from the children from the beginning of November 2000 through May 2001. Virtually in each week between mid-November and the end of April (a period of 24 weeks), influenza viruses accounted for at least 5% of all respiratory infections in the children. During the peak of the epidemic, the percentage of influenza-positive children exceeded 20%. CONCLUSIONS: This study confirms the important role of influenza as a cause of acute respiratory infections in children, even in winters of mild or moderate influenza activity. The study also shows that influenza viruses may circulate in the community at substantial levels much longer than previously thought.


Assuntos
Surtos de Doenças , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/epidemiologia , Doença Aguda , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Finlândia/epidemiologia , Humanos , Incidência , Influenza Humana/diagnóstico , Masculino , Estudos Prospectivos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Fatores de Risco , Distribuição por Sexo
18.
Hum Mutat ; 20(6): 480-1, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12442285

RESUMO

Mutations in the gene encoding Bruton tyrosine kinase (BTK) result in X-linked agammaglobulinemia (XLA), an immunodeficiency of antibody defect. By using base excision sequence scanning method (BESS) followed by direct sequencing we found in seven unrelated families with a classical XLA phenotype various mutations including six novel mutations (g.64512_64513insC, c.108_109insG, c.1700_1701insACTACAG, g.51375_51376GC>TG, g.63991_63992insGGTAGAAAAAA, c.1956_1957insCA) and a previously known silent polymorphism (c.2031C>T). Except for two mutations, the alterations affect the kinase domain. There was exceptionally high proportion of insertions in the cohort. Frameshift insertion was found altogether in five patients, three of which are on introns, one in upstream region, and one in exon 18 leading to frameshift mutation and truncation of the protein. In the intron 4 there is a substitution of two bases. Carrier detection was performed in four families. In one case the mutation was found to be de novo.


Assuntos
Agamaglobulinemia/genética , Proteínas Tirosina Quinases/genética , Cromossomo X/genética , Tirosina Quinase da Agamaglobulinemia , Agamaglobulinemia/enzimologia , Sequência de Bases , Pré-Escolar , Análise Mutacional de DNA/métodos , Evolução Fatal , Ligação Genética , Humanos , Lactente , Masculino , Mutagênese Insercional , Mutação
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