Human severe combined immunodeficiency: Genetic, phenotypic, and functional diversity in one hundred eight infants

Buckley, Rebecca H.; Schiff, Richard I.; Schiff, Sherrie E.; Markert, M. Louise; Williams, Larry W.; Harville, Terry; Roberts, Joseph L.; Puck, Jennifer M.

doi:10.1016/s0022-3476(97)70199-9

Cited by 502 publications

(297 citation statements)

References 38 publications

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“…SCID patients can be divided into two main categories: those with TÀB þ SCID (70%), generally resulting from a T-cell signaling defect and those with TÀBÀ SCID (30%), mostly due to a defect in recombination of the variable (V), diversity (D) and joining (J) gene segments. 4,5 Differentiation of lymphoid precursors to mature B and T lymphocytes requires the rearrangement and expression of genes encoding the Ig or T-cell receptors. V(D)J gene segments are recombined to form a functional V(D)J exon.…”

Section: Introductionmentioning

confidence: 99%

Artemis splice defects cause atypical SCID and can be restored in vitro by an antisense oligonucleotide

IJspeert

Lankester

et al. 2011

Genes Immun

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Artemis deficiency is known to result in classical TÀBÀ severe combined immunodeficiency (SCID) in case of Artemis null mutations, or Omenn's syndrome in case of hypomorphic mutations in the Artemis gene. We describe two unrelated patients with a relatively mild clinical TÀBÀ SCID phenotype, caused by different homozygous Artemis splice-site mutations. The splice-site mutations concern either dysfunction of a 5 0 splice-site or an intronic point mutation creating a novel 3 0 splice-site, resulting in mutated Artemis protein with residual activity or low levels of wild type (WT) Artemis transcripts. During the first 10 years of life, the patients suffered from recurrent infections necessitating antibiotic prophylaxis and intravenous immunoglobulins. Both mutations resulted in increased ionizing radiation sensitivity and insufficient variable, diversity and joining (V(D)J) recombination, causing B-lymphopenia and exhaustion of the naive T-cell compartment. The patient with the novel 3 0 splice-site had progressive granulomatous skin lesions, which disappeared after stem cell transplantation (SCT). We showed that an alternative approach to SCT can, in principle, be used in this case; an antisense oligonucleotide (AON) covering the intronic mutation restored WT Artemis transcript levels and non-homologous end-joining pathway activity in the patient fibroblasts.

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Section: Introductionmentioning

confidence: 99%

Artemis splice defects cause atypical SCID and can be restored in vitro by an antisense oligonucleotide

IJspeert

Lankester

et al. 2011

Genes Immun

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“…[1][2][3] For example, 12 different genotypes have been identified for severe combined immunodeficiency (SCID; Table I). [4][5][6][7][8] However, advances in finding the causes and explaining the pathophysiology of PIs have not yet been paralleled with similar progress in the development of safe and curative treatments. Patients with immunodeficiency have experienced considerable benefit from medical advances in supportive therapy, including the prophylaxis and treatment of infections, the management of chronic respiratory and gastrointestinal diseases, and the treatment of secondary neoplasias.…”

mentioning

confidence: 99%

Successes and risks of gene therapy in primary immunodeficiencies

Chinen

Puck

2004

Journal of Allergy and Clinical Immunology

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“…These disorders are rare, with a frequency ranging from one in 50 000 to one in 500 000 births. 1 Clinical signs and symptoms commonly manifest by 6 months of age and include failure to thrive, oral thrush, candidal diaper rash, recurrent respiratory infections, cutaneous graft-versus-host disease (GVHD) and oral and genital ulcerations. The nonspecific clinical findings and the significant degree of variability among patients often complicate and delay the diagnosis.…”

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confidence: 99%

“…The profound lack in immune function leads to infections usually fatal in infancy unless the immune system can be reconstituted. 1 Currently, hematopoietic stem cell transplantation from a variety of sources including bone marrow, peripheral or umbilical cord blood is the primary modality of treatment of SCID, 2 although the early results of gene therapy are encouraging. 3 The major cutaneous manifestations of SCID are skin and mucosal infections, eczematous rashes and GVHD.…”

mentioning

confidence: 99%

Cutaneous manifestations of maternal engraftment in patients with severe combined immunodeficiency: a clinicopathologic study

Denianke

Frieden

Cowan

et al. 2001

Bone Marrow Transplant

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Summary:SCID is a heterogeneous group of disorders characterized by defective T cell and B cell function. Eczematous and morbilliform eruptions are common, and graft-versus-host disease (GVHD) due to maternal engraftment has been documented. We sought to better characterize SCID-related cutaneous disease observed prior to BMT and to compare the eruption to conventional GVHD. Medical records of 51 patients with SCID treated between 1982 and 1999 were reviewed. Ten of 51 (20%) had rash and evidence of maternal engraftment prior to BMT (study group). Eleven of 51 (22%) had no rash or evidence of engraftment pre-BMT but developed GVHD following transplant (control group). Skin biopsies were available for review for 8/10 of the study group and for 8/11 of the control group. Cutaneous findings consisted of a scaling, erythematous maculopapular eruption spread widely over the trunk and extremities, with near-erythroderma in some patients. Microscopically, biopsies from the study group differed significantly from controls. Key differences included parakeratosis (P р 0.01), psoriasiform hyperplasia (P р 0.04) and spongiosis (P р 0.04). The dermatopathologic findings of transplacental GVHD differ from the pattern of post-transplant GVHD. A 'psoriasiform-lichenoid-spongiotic' pattern with necrotic keratinocytes should trigger consideration of SCID and maternal engraftment in the dermatopathologic evaluation of eruptions of infancy. Bone Marrow Transplantation (2001) 28, 227-233. Keywords: severe combined immunodeficiency disease (SCID); bone marrow transplant (BMT); graft-versus-host disease (GVHD); maternal engraftment Severe combined immunodeficiency diseases (SCIDs) are a heterogeneous group of genetic disorders characterized by deficiency of both T and B cell functions. The mode of

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Human severe combined immunodeficiency: Genetic, phenotypic, and functional diversity in one hundred eight infants

Cited by 502 publications

References 38 publications

Artemis splice defects cause atypical SCID and can be restored in vitro by an antisense oligonucleotide

Artemis splice defects cause atypical SCID and can be restored in vitro by an antisense oligonucleotide

Successes and risks of gene therapy in primary immunodeficiencies

Cutaneous manifestations of maternal engraftment in patients with severe combined immunodeficiency: a clinicopathologic study

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