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1.
J Eur Acad Dermatol Venereol ; 33(7): 1412-1420, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30869812

RESUMO

BACKGROUND: Paediatric cutaneous granuloma with primary immunodeficiency (PID) is a rare condition. The physiopathology is unclear, and treatment is challenging. We report on 17 paediatric cases and review the literature. OBJECTIVES: To make dermatologists and dermatopathologists aware of the diagnostic value of skin granulomas in paediatric PID. METHODS: We collected data on 17 patients with cutaneous granulomas and PID registered with us and also reviewed 33 cases from the literature. RESULTS: Cutaneous granuloma was the presenting feature of the PID in 15 of the 50 collated cases. The lesions presented as red-brownish nodules and infiltrated ulcerative plaques, predominantly on the face and limbs. Scleroderma-like infiltration on a single limb was observed in 10% of the cases. The associated PID was ataxia-telangiectasia (52%), combined immunodeficiency (24%), cartilage-hair hypoplasia (6%) and other subtypes (18%). The granulomas were mostly sarcoidal, tuberculoid, palisaded or undefined subtypes. In some patients, several different histopathologic granulomatous patterns were found in the same biopsy. Some granulomas were associated with the presence of a vaccine strain of rubella virus. CONCLUSION: Cutaneous granulomas associated with a PID have a variable clinical presentation. A PID can be suspected when crusty, brownish lesions are found on the face or limbs. The concomitant presence of several histological subtypes in a single patient is suggestive of a PID.

2.
Clin Transl Gastroenterol ; 9(10): 201, 2018 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-30385752

RESUMO

OBJECTIVE: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is an autoimmune disease caused by mutations in the forkhead box protein 3 gene (FOXP3), which encodes a key regulator of immune tolerance. The aim of this study was to describe the clinical heterogeneity of the disease in a national French cohort. METHODS: Multicenter retrospective study of patients diagnosed with IPEX syndrome caused by mutations in FOXP3. RESULTS: Thirty children from 26 families were included. Age at disease onset (median [first to third quartile]) was 1.5 mo [0-84] and at death 3.5 years [0-10.5] (n = 15) indicating a high heterogeneity. Initial presentation was diarrhoea (68%), type 1 diabetes (T1D; 25%), skin lesions (7%) and nephropathy (3%). During the course of the disease the following main symptoms were observed: diarrhoea (100%), skin lesions (85%), T1DM (50%), severe food allergies (39%), haematological disorders (28%), nephropathies (25%), hepatitis (14%) as well as the presence of a variety of autoantibodies. Immunosuppressive mono- or combination therapy led to improvement in eight children. Three boys displayed a stable disease course without any immunosuppressive medication. Overall 10-year survival rate was 43% (42% in transplanted patients and 52% in patients on immunosuppressive therapy). Five out of 22 identified FOXP3 mutations have not been described yet: c.-23 + 1G > A, c.-23 + 5G > A, c.264delC, c.1015C > T and c.1091A > G. The first two produced atypical, attenuated phenotypes. Missense and frameshift mutations affecting the forkhead domain were associated with poor survival (Gehan-Wilcoxon p = 0.002). CONCLUSION: The broad phenotypic heterogeneity of IPEX raises questions about modifying factors and justifies early FOXP3 sequencing in suspected cases.

3.
J Allergy Clin Immunol ; 141(1): 322-328.e10, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28392333

RESUMO

BACKGROUND: Rare DNA breakage repair disorders predispose to infection and lymphoreticular malignancies. Hematopoietic cell transplantation (HCT) is curative, but coadministered chemotherapy or radiotherapy is damaging because of systemic radiosensitivity. We collected HCT outcome data for Nijmegen breakage syndrome, DNA ligase IV deficiency, Cernunnos-XRCC4-like factor (Cernunnos-XLF) deficiency, and ataxia-telangiectasia (AT). METHODS: Data from 38 centers worldwide, including indication, donor, conditioning regimen, graft-versus-host disease, and outcome, were analyzed. Conditioning was classified as myeloablative conditioning (MAC) if it contained radiotherapy or alkylators and reduced-intensity conditioning (RIC) if no alkylators and/or 150 mg/m2 fludarabine or less and 40 mg/kg cyclophosphamide or less were used. RESULTS: Fifty-five new, 14 updated, and 18 previously published patients were analyzed. Median age at HCT was 48 months (range, 1.5-552 months). Twenty-nine patients underwent transplantation for infection, 21 had malignancy, 13 had bone marrow failure, 13 received pre-emptive transplantation, 5 had multiple indications, and 6 had no information. Twenty-two received MAC, 59 received RIC, and 4 were infused; information was unavailable for 2 patients. Seventy-three of 77 patients with DNA ligase IV deficiency, Cernunnos-XLF deficiency, or Nijmegen breakage syndrome received conditioning. Survival was 53 (69%) of 77 and was worse for those receiving MAC than for those receiving RIC (P = .006). Most deaths occurred early after transplantation, suggesting poor tolerance of conditioning. Survival in patients with AT was 25%. Forty-one (49%) of 83 patients experienced acute GvHD, which was less frequent in those receiving RIC compared with those receiving MAC (26/56 [46%] vs 12/21 [57%], P = .45). Median follow-up was 35 months (range, 2-168 months). No secondary malignancies were reported during 15 years of follow-up. Growth and developmental delay remained after HCT; immune-mediated complications resolved. CONCLUSION: RIC HCT resolves DNA repair disorder-associated immunodeficiency. Long-term follow-up is required for secondary malignancy surveillance. Routine HCT for AT is not recommended.

4.
Arch Pediatr ; 23(4): 389-93, 2016 Apr.
Artigo em Francês | MEDLINE | ID: mdl-26850155

RESUMO

Malignant infantile osteopetrosis is a rare congenital disease characterized by a dysfunction of osteoclasts followed by an abnormal bone densification. We report the case of a 5-month-old infant in whom this disease was suspected because of the clinical (hepatosplenomegaly, gingival hypertrophy), hematological (pancytopenia and hypocalcemia), and radiological criteria (abnormal bone density, periosteal reaction). The genetic investigation confirmed the diagnosis. Compound heterozygous mutations in the CLCN7 gene were identified, including an as yet undescribed mutation. The second mutation had already been described as being responsible for severe and irreversible neurological damage in patients with osteopetrosis. Since this patient presented severely delayed development, he was not eligible for bone marrow transplantation.


Assuntos
Osteopetrose , Humanos , Lactente , Masculino , Mutação , Osteopetrose/diagnóstico , Osteopetrose/genética , Fenótipo
5.
Med Mal Infect ; 45(6): 189-98, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26026226

RESUMO

Invasive aspergillosis (IA) is a major cause of morbidity and mortality in immunocompromised adults and children, the number of which has been continuously increasing in the last decades. The purpose of our review was to provide epidemiological, clinical, and biological data and antifungal treatment options in the pediatric population. Several biological assays (galactomannan enzyme immunoassay, ß-D-glucan, detection of Aspergillus spp. DNA) have proven useful adjuncts for the diagnosis of IA in adult studies. However, data on these assays in children is limited by small sample sizes and sometimes conflicting results concerning their sensitivity/specificity. Pediatric treatment recommendations are mainly extrapolated from results of clinical trials performed in adults. It is thus necessary to develop new antifungal formulations specifically adapted to the pediatric population and to evaluate their pharmacokinetic/pharmacodynamic profile, their safety, and their effectiveness in infants and children.


Assuntos
Aspergilose , Fungemia , Adolescente , Antifúngicos/uso terapêutico , Antígenos de Fungos/sangue , Antineoplásicos/efeitos adversos , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergilose/epidemiologia , Aspergilose/prevenção & controle , Aspergillus/efeitos dos fármacos , Aspergillus/imunologia , Aspergillus/isolamento & purificação , Criança , Pré-Escolar , DNA Fúngico/sangue , Fungemia/diagnóstico , Fungemia/tratamento farmacológico , Fungemia/epidemiologia , Fungemia/prevenção & controle , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Lactente , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/microbiologia , Guias de Prática Clínica como Assunto , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
6.
Eur J Clin Microbiol Infect Dis ; 33(4): 545-50, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24078025

RESUMO

Scarce data exist on allogeneic hematopoietic stem cell transplantation (HSCT) outcomes in hepatitis B virus (HBV)-naïve recipients from HBV-experienced donors. Long-term follow-up is herein reported for 17 allogeneic HSCT performed in 13 HBV-naïve children from HBc-antibodies-positive donors between 2006 and 2012. Four donors were HBs-antigen-positive, with detectable but low viremia in 2 cases (<2 log10IU/ml). HBV-DNA was undetectable in all transplanted cell products. Recipients' HBV prophylaxis consisted of pre-transplant vaccination, polyvalent immune globulins, specific anti-HBV immune globulins, and/or oral lamivudine in 3, 12, 8, and 8 children, respectively. No case of HBV transmission occurred based on negative close monitoring of recipients' HBV serology and plasma HBV-DNA during a median follow-up of 22 months. In case of undetectable viremia in the donor, prophylaxis with vaccination and/or immune globulins in the recipient seems to be sufficient and lamivudine prophylaxis might be unnecessary to prevent viral transmission. In case of undetectable viremia in the donor, a systematic screening of HBV DNA in the stem cell product might be unnecessary to confirm the low risk of viral transmission. Prior exposure to HBV in the donor should not be considered a contraindication to HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/normas , Anticorpos Anti-Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Doadores de Tecidos/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Viremia/sangue
7.
Neurology ; 78(15): 1150-6, 2012 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-22422896

RESUMO

OBJECTIVES: To differentiate onset of CNS involvement in primary hemophagocytic lymphohistiocytosis (HLH) from that of other CNS inflammatory diseases and to identify early symptoms linked to abnormal cognitive outcome. METHODS: Forty-six children with primary HLH who had neurologic evaluation within 2 weeks and brain MRI within 6 months of diagnosis were included. Initial symptoms, CSF study, brain MRI, and neurologic outcome were assessed. Brain MRIs were compared with those of 44 children with acute disseminated encephalomyelitis (ADEM). RESULTS: At disease onset, 29 children (63%) had neurologic symptoms and 7 (15%) had microcephaly. Twenty-three (50%) children had abnormal CSF study, but only 15 (33%) had abnormal brain MRI. The latter showed that patients with HLH, unlike patients with ADEM, had symmetric periventricular lesions, without thalamic and brainstem involvement and with infrequent hyposignal intensity on T1. At the end of follow-up (3.6 ± 3.6 years), 17 of the 28 (61%) surviving patients had normal neurologic status, 5 (18%) had a severe neurologic outcome, and 6 (21%) had mild cognitive difficulties. Abnormal neurologic outcome was not influenced by age or type of genetic defect, but by the presence of neurologic symptoms, MRI lesions, or abnormal CSF study at onset. Early clinical and MRI symptoms may regress after treatment. CONCLUSION: Neurologic symptoms are frequent at the onset of primary HLH and are mostly associated with abnormal CSF findings, but with normal brain MRI. In cases of abnormal brain MRI, the observed lesions differ from those of ADEM.


Assuntos
Encéfalo/patologia , Encéfalo/fisiopatologia , Linfo-Histiocitose Hemofagocítica/patologia , Linfo-Histiocitose Hemofagocítica/fisiopatologia , Adolescente , Líquido Cefalorraquidiano/metabolismo , Criança , Pré-Escolar , Transtornos da Consciência/etiologia , Diagnóstico Diferencial , Encefalomielite Aguda Disseminada/patologia , Encefalomielite Aguda Disseminada/fisiopatologia , Feminino , Seguimentos , Humanos , Lactente , Linfo-Histiocitose Hemofagocítica/líquido cefalorraquidiano , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/psicologia , Imagem por Ressonância Magnética , Masculino , Registros Médicos , Meningismo/etiologia , Microcefalia/etiologia , Microcefalia/patologia , Microcefalia/fisiopatologia , Estudos Retrospectivos , Convulsões/etiologia , Resultado do Tratamento
8.
Bone Marrow Transplant ; 36(2): 107-14, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15908971

RESUMO

We retrospectively analyzed the outcome of hematopoietic stem cell transplantations (HSCT) performed at our Center between 1991 and 2002 in 11 unselected patients with Omenn syndrome, a variant of severe combined immunodeficiency. The patients' mean age at the time of the first HSCT was 8.4 months. Two patients received two, and one patient three, HSCT procedures. The resulting 15 HSCT derived in seven cases from HLA-haploidentical parents, in four patients from matched unrelated donors, in three cases from an HLA phenotypically identical related donor, and in one case from an HLA genotypically identical family donor. Nine out of 11 patients are alive and immunoreconstituted 30-146 months after transplantation. At the time of the most recent evaluation, all of the nine survivors had normal T-cell function, and eight of them had developed normal antibody production. This study demonstrates an overall mortality of 18.2%, which is substantially lower than previously reported. Early recognition of OS, rapid initiation of adequate supportive treatment and HSCT lead to improved outcome for this otherwise fatal disease, regardless of the origin and matching of hematopoietic stem cells.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Sarcoma Histiocítico/terapia , Adulto , Idoso , Pré-Escolar , Intervalo Livre de Doença , Sarcoma Histiocítico/metabolismo , Sarcoma Histiocítico/mortalidade , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Estudos Retrospectivos , Síndrome , Linfócitos T/metabolismo , Transplante Homólogo , Resultado do Tratamento
9.
Eur J Med Res ; 7(4): 177-80, 2002 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-12010653

RESUMO

Screening for Aspergillus antigen and DNA has been introduced for the early diagnosis of invasive aspergillosis (IA) in adults, but data in children at risk are scarce. Seventeen 1-108 month-old children were screened for Aspergillus antigenaemia by a commercial assay before and after bone marrow transplantation (BMT). Seventy-one serum samples were examined retrospectively by a novel nested PCR assay. Results of both assays were correlated with clinical, radiological and microbiological findings used for the definition of invasive aspergillosis by the European Organisation for Research and Treatment of Cancer (EORTC). Three cases of probable or possible IA were defined, and in 14 children invasive aspergillosis was ruled out. In 10 children, Aspergillus antigen was detected in at least two consecutive serum samples, a microbiological EORTC criteria of IA. Specific DNA was detected in 8 antigen-positive and 2 antigen-negative sera. A positive predictive value of 20% was calculated for both assays. Hence, a high rate of positive results of antigen Elisa and PCR assays in BMT children are due to transient antigenaemia and fungaemia without clinical relevance. According to our data, prospective studies in well defined pediatric patients are urgently needed to determine the value of serial Aspergillus PCR assays for the early diagnosis of invasive aspergillosis in children at risk.


Assuntos
Antígenos de Fungos/sangue , Aspergillus/isolamento & purificação , Transplante de Medula Óssea/efeitos adversos , DNA Fúngico/sangue , Aspergilose/diagnóstico , Aspergilose/etiologia , Aspergilose/microbiologia , Aspergillus/genética , Aspergillus/imunologia , Criança , Pré-Escolar , DNA Fúngico/genética , Feminino , Genes Fúngicos , Humanos , Lactente , Masculino , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Estudos Retrospectivos
10.
Cell ; 105(2): 177-86, 2001 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-11336668

RESUMO

The V(D)J recombination process insures the somatic diversification of immunoglobulin and antigen T cell receptor encoding genes. This reaction is initiated by a DNA double-strand break (dsb), which is resolved by the ubiquitously expressed DNA repair machinery. Human T-B-severe combined immunodeficiency associated with increased cellular radiosensitivity (RS-SCID) is characterized by a defect in the V(D)J recombination leading to an early arrest of both B and T cell maturation. We previously mapped the disease-related locus to the short arm of chromosome 10. We herein describe the cloning of the gene encoding a novel protein involved in V(D)J recombination/DNA repair, Artemis, whose mutations cause human RS-SCID. Protein sequence analysis strongly suggests that Artemis belongs to the metallo-beta-lactamase superfamily.


Assuntos
Linfócitos B/fisiologia , Reparo do DNA/genética , Proteínas Nucleares , Tolerância a Radiação/genética , Recombinação Genética/genética , Imunodeficiência Combinada Severa/genética , Linfócitos T/fisiologia , beta-Lactamases/genética , Sequência de Aminoácidos , Sequência de Bases , Northern Blotting , Células Cultivadas , Cromossomos Humanos Par 10/genética , Clonagem Molecular , Endonucleases , Fibroblastos , Humanos , Dados de Sequência Molecular , Mutação , Estrutura Terciária de Proteína , Alinhamento de Sequência , Imunodeficiência Combinada Severa/fisiopatologia , Transfecção , beta-Lactamases/química , beta-Lactamases/metabolismo
11.
Blood ; 97(9): 2772-6, 2001 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-11313270

RESUMO

Omenn syndrome (OS) is an inherited disorder characterized by an absence of circulating B cells and an infiltration of the skin and the intestine by activated oligoclonal T lymphocytes, indicating that a profound defect in the lymphoid developmental program could be accountable for this condition. Inherited mutations in either the recombination activating genes RAG1 or RAG2, resulting in partial V(D)J recombinase activity, were shown to be responsible for OS. This study reports on the characterization of new RAG1/2 gene mutations in a series of 9 patients with OS. Given the occurrence of the same mutations in patients with T-B-severe combined immune deficiency or OS on 3 separate occasions, the proposal is made that an additional factor may be required in certain circumstances for the development of the Omenn phenotype. The nature of this factor is discussed.


Assuntos
Proteínas de Ligação a DNA , Genes RAG-1 , Mutação , Imunodeficiência Combinada Severa/genética , DNA Nucleotidiltransferases/genética , DNA Nucleotidiltransferases/metabolismo , Feminino , Regulação Enzimológica da Expressão Gênica/imunologia , Humanos , Lactente , Masculino , Proteínas Nucleares , Imunodeficiência Combinada Severa/enzimologia , Imunodeficiência Combinada Severa/etiologia , Síndrome , VDJ Recombinases
12.
J Biol Chem ; 275(17): 12672-5, 2000 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-10777560

RESUMO

The V(D)J recombination, which leads to the somatic rearrangement of variable, diversity, and joining segments, is the mechanism accountable for the diversity of T cell receptor- and Ig-encoding genes. The products of the RAG1 and RAG2 genes are the lymphoid-specific factors responsible for the initiation of the V(D)J recombination through the generation of a DNA double strand break. RAG1 or RAG2 gene inactivation in the mouse leads to abortion of the V(D)J rearrangement process, early block in both T and B cell maturation, and, ultimately, to severe combined immune deficiency (SCID). A human SCID condition is also characterized by an absence of mature T and B lymphocytes and is associated with mutations in either RAG1- or RAG2-encoding genes. Based on the predicted beta-propeller three-dimensional structure model for RAG2, we found that six out of the seven mutations described to date in T-B-SCID patients are clustered on one side of the propeller, in regions exposed to solvent. This finding reinforces the biological significance of this predicted model and suggests that RAG1 interacts with RAG2 on one of the side of the scaffold formed by the beta-propeller.


Assuntos
Proteínas de Ligação a DNA/genética , Mutação , Imunodeficiência Combinada Severa/genética , Sequência de Aminoácidos , Western Blotting , Linhagem Celular Transformada , Clonagem Molecular , DNA Nucleotidiltransferases/metabolismo , Proteínas de Ligação a DNA/química , Fibroblastos/metabolismo , Genes RAG-1/genética , Células HeLa , Proteínas de Homeodomínio/química , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Família Multigênica , Proteínas Nucleares , Fenótipo , Estrutura Terciária de Proteína , Recombinação Genética , Análise de Sequência de DNA , VDJ Recombinases
13.
Hum Mol Genet ; 9(4): 583-8, 2000 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-10699181

RESUMO

V(D)J recombination, accountable for the diversity of T cell receptor- and immunoglobulin-encoding genes, is initiated by a lymphoid-specific DNA double-strand break. The general DNA repair machinery is responsible for the resolution of this break. Any defect in one of the known components of the DNA repair/V(D)J recombination machinery (Ku70, Ku80, DNA-PKcs, XRCC4 and DNA ligase IV) leads to abortion of the V(D)J rearrangement process, early block in both T and B cell maturation, and ultimately to severe combined immune deficiency (SCID) in several animal models. A human SCID condition is also characterized by an absence of mature T and B lymphocytes, and is associated with an increase in sensitivity to DNA-damaging agents (RS-SCID). None of the above-mentioned genes are defective in these patients, arguing for the likelihood of the existence of yet another unknown component of the V(D)J recombination/DNA repair apparatus. Athabascan-speaking (SCIDA) Navajo and Apache Native Americans have a very high incidence of T(-)B(-)SCID. The SCIDA locus is highly linked with markers on chromosome 10p, although the exact molecular defect has not been recognized in these patients. We show here that cells with the SCIDA defect are impaired in the DNA repair phase of V(D)J recombination similarly to RS-SCID, precisely an absence of V(D)J coding joint formation. Moreover, genotyping analysis in several RS-SCID families corroborates a linkage of the RS-SCID locus to the SCIDA region on chromosome 10p. These results demonstrate the presence of a new essential DNA repair/V(D)J recombination gene in this region, the mutation of which causes RS-SCID in humans.


Assuntos
Cromossomos Humanos Par 10/genética , Dano ao DNA , Reparo do DNA , DNA/genética , Integrases , Recombinação Genética , Imunodeficiência Combinada Severa/genética , Células Cultivadas , DNA Nucleotidiltransferases/genética , Fibroblastos/enzimologia , Ligação Genética , Marcadores Genéticos , Humanos , Região Variável de Imunoglobulina/genética , Linhagem , Receptores de Antígenos de Linfócitos T/genética , Recombinases , Imunodeficiência Combinada Severa/enzimologia , Imunodeficiência Combinada Severa/patologia
14.
J Exp Med ; 188(4): 627-34, 1998 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-9705945

RESUMO

The products of recombination activating gene (RAG)1 and RAG2 initiate the lymphoid-specific phase of the V(D)J recombination by creating a DNA double-strand break (dsb), leaving hairpin-sealed coding ends. The next step uses the general DNA repair machinery of the cells to resolve this dsb. Several genes involved in both V(D)J recombination and DNA repair have been identified through the analysis of in vitro mutants (Chinese hamster ovary cells) and in vivo situations of murine and equine severe combined immunodeficiency (scid). These studies lead to the description of the Ku-DNA-dependent protein kinase complex and the XRCC4 factor. A human SCID condition is characterized by an absence of B and T lymphocytes. One subset of these patients also demonstrates an increased sensitivity to the ionizing radiation of their fibroblasts and bone marrow precursor cells. This phenotype is accompanied by a profound defect in V(D)J recombination with a lack of coding joint formation, whereas signal joints are normal. Functional and genetic analyses distinguish these patients from the other recombination/repair mutants, and thus define a new group of mutants whose affected gene(s) is involved in sensitivity to ionizing radiation and V(D)J recombination.


Assuntos
Antígenos Nucleares , Linfócitos B/imunologia , DNA Helicases , Reparo do DNA , Rearranjo Gênico , Genes de Imunoglobulinas , Tolerância a Radiação , Imunodeficiência Combinada Severa/imunologia , Linfócitos T/imunologia , Animais , Linhagem Celular , Linhagem Celular Transformada , Cricetinae , Cricetulus , Reparo do DNA/efeitos da radiação , Proteína Quinase Ativada por DNA , Proteínas de Ligação a DNA/metabolismo , Feminino , Raios gama , Rearranjo Gênico/efeitos da radiação , Humanos , Região de Junção de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Autoantígeno Ku , Ligantes , Masculino , Proteínas Nucleares/metabolismo , Linhagem , Proteínas Serina-Treonina Quinases/metabolismo , Imunodeficiência Combinada Severa/genética
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