1/68. Combined immunodeficiency associated with increased apoptosis of lymphocytes and radiosensitivity fibroblasts.Severe immunodeficiency characterized by lymphopenia was found in two siblings, one of whom was examined in detail. The calcium flux, pattern of tyrosine phosphorylation of proteins, and interleukin 2 (IL-2) production and proliferation in response to mitogens suggested that the peripheral blood T cells activated normally. The peripheral blood T cells were shown to have an activated phenotype with increased expression of CD45RO and CD95/Fas. Increased spontaneous apoptosis occurred in unstimulated lymphocyte cultures. The elevated apoptosis was not due to alterations in expression or to mutations in Bcl-2, Bcl-X(L), or Flip, nor could the spontaneous apoptosis be prevented by blocking Fas, suggesting that it was independent of Fas signaling. This is the first inherited combined immunodeficiency associated with impaired lymphocyte survival. fibroblasts derived from the patient showed appreciable radiosensitivity in clonal assays, but apoptosis was not elevated. Our results show that the fibroblasts represent a new radiosensitive phenotype not associated with cell cycle checkpoint defects, V(D)J recombination defects, or elevated chromosome breakage. We suggest that the affected gene plays a role in an undetermined damage response mechanism that results in elevated spontaneous apoptosis in lymphoid cells and radiosensitivity in fibroblasts.- - - - - - - - - - ranking = 1keywords = breakage, chromosome (Clic here for more details about this article) |
2/68. Accelerated phase in partial albinism with immunodeficiency (Griscelli syndrome): genetics and stem cell transplantation in a 2-month-old girl.A 2-month-old girl presented with fever, hepatosplenomegaly, pancytopenia, hypertriglyceridaemia and silvery-greyish hair, suggesting the diagnosis of Griscelli syndrome (partial albinism with immunodeficiency). This diagnosis was confirmed by the characteristic agglomeration of melanin in the hair shaft and accumulation of melanosomes in melanocytes of the skin. The patient was homozygous for polymorphic markers around the myosin-Va gene on chromosome 15q21, which co-localize to the Griscelli disease locus. Natural-killer cells were in the lower range. The stimulation of lymphocytes with antigen and mitogen was normal. The patient's accelerated phase, characterized by haemophagocytosis was treated with prednisolone, rabbit anti-thymocyte globulins, and intrathecal methotrexate. Remission was maintained with cyclosporin A until HLA-compatible peripheral blood stem cell transplantation from her mother. CONCLUSION: The silvery-greyish hair associated with fever, pancytopenia and hypertriglyceridaemia is the clue to early diagnosis of Griscelli syndrome and important to prevent death before stem cell transplantation.- - - - - - - - - - ranking = 0.043619741980639keywords = chromosome (Clic here for more details about this article) |
3/68. Early prenatal diagnosis of the ICF syndrome.The ICF syndrome (immunodeficiency, (para)centromeric instability and facial abnormalities) is a rare autosomal recessive disorder with characteristic cytogenetic aberrations of chromosomes 1, 9 and 16 in lymphocytes. Previously, only one case has been diagnosed prenatally in the second trimester of pregnancy by fetal blood sampling. We report the first early prenatal exclusion of the ICF syndrome by chorionic villous sampling (CVS) and linkage analysis in a family with a previous affected child. The fetus was heterozygous for marker D20S850 closely linked to the ICF locus. The family was counselled of a probability of over 90% that the fetus would be unaffected. Postnatal chromosome analysis on peripheral blood was normal and thus confirmed the prenatal diagnosis.- - - - - - - - - - ranking = 0.087239483961279keywords = chromosome (Clic here for more details about this article) |
4/68. Clinical and immunological spectrum of partial digeorge syndrome.We present four cases of digeorge syndrome diagnosed at our center. Onset occurred during the neonatal period and was associated with severe congenital heart disease. In case 1, the patient had heart disease and absence of thymus. Total t-lymphocytes were 34%; total T4-lymphocytes were 27%. Stimulation test with phytohemagglutinin (PHA), concanavalin a (conA) and pokeweed mitogen were negative. Microdeletion was found in the chromosome 22q11 region. The second case involved heart disease, microstomia, round and rotated ears and branchial cyst. Total t-lymphocytes were 38% and total T4-lymphocytes 27%. Thymus was absent. Microdeletion in the chromosome 22q11 region. Case 3 showed heart disease, renal malformation, absence of thymus and parathyroid gland. The patient died 5 days postsurgery. Microdeletion was seen at chromosome 22q11. In the fourth case there was heart disease, microretrognathia, hypertelorism, short neck, absence of thymus and parathyroid glands. Total t-lymphocytes were 22%, total T4-lymphocytes 15%, and total T lymphocytes for pokeweed mitogen were negative. Microdeletion was found at chromosome 22q11. At the age of 13 days the patient died. The cases were recorded during a 2-year period, between 1997 and 1998. The prevalence of digeorge syndrome in the number of admissions for congenital heart disease among the neonates at our hospital was 3.14%. Presentation in the form of repeated infections is rare, since most cases of digeorge syndrome are partial, and functional cellular immunity is preserved.- - - - - - - - - - ranking = 0.17447896792256keywords = chromosome (Clic here for more details about this article) |
5/68. Juvenile rheumatoid arthritis-like polyarthritis in nijmegen breakage syndrome.nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease (8q21) from the family of the genetically determined chromosomal instability syndromes. The disorder is characterized by microcephaly, growth retardation, immunodeficiency, and high incidence of cancer. Several noninflammatory anomalies of the musculoskeletal system have been described in patients with this syndrome. We describe an Argentinian girl with all the clinical, immunological, and cytogenic characteristics described for NBS plus a juvenile rheumatoid arthritis-like syndrome. To our knowledge this is the first report of a patient with the NBS who presented with a symmetric chronic polyarthritis resembling JRA.- - - - - - - - - - ranking = 4.7819012900968keywords = breakage (Clic here for more details about this article) |
6/68. Griscelli syndrome: rare neonatal syndrome of recurrent hemophagocytosis.Griscelli syndrome (GS) is a rare inherited disease characterized by immunodeficiency and partial albinism. The microscopic findings of the skin and hair are highly suggestive of the disease. The GS locus colocalizes on chromosome 15q21 with the myosin-Va gene (MYO5a), and mutations have been identified in few patients. We describe a 2-month-old Hispanic girl with severe pancytopenia secondary to hemophagocytosis. Even though a mutation at the Griscelli locus had not been identified, her clinical features and outcome were typical of GS. The purpose of this article is to alert physicians to the association between GS and hemophagocytosis. We suggest that GS should be considered in infants with hemophagocytosis because the features of partial albinism can be subtle. The relevant literature is summarized.- - - - - - - - - - ranking = 0.043619741980639keywords = chromosome (Clic here for more details about this article) |
7/68. T-cell prolymphocytic leukemia with autoimmune manifestations in nijmegen breakage syndrome.nijmegen breakage syndrome (NBS) is characterized by growth retardation, microcephaly, mental retardation, immunodeficiency, and predisposition to malignancies, especially B-cell lymphomas. In contrast, leukemia is rare. A 23-year-old NBS patient presented with anemia, thrombocytopenia, and hyperlymphocytosis. The diagnosis of T-cell prolymphocytic leukemia (T-PLL) was confirmed by cytological and immunological assays (TdT(-), CD2( ), CD5( ), CD3m, and CD7( )). Biological assays also showed a hemolytic anemia and a clotting factor V decrease. The patient was first treated by methylprednisone for 3 weeks. During this period the lymphocyte count decreased. The simultaneous normalization of the hemolysis and of factor V suggested that both could be related to T-PLL. Since T-PLL is refractory to conventional therapies with a poor prognosis, an intensive chemotherapy such as 2'-deoxycoformycin with anti-CDw52 monoclonal antibodies is usually favored. In the present case, however, because of the specific context (i.e., NBS-induced immunodepression, severe hemolytic anemia, and acquired factor v deficiency), he received pentostatin weekly during 1 month and in maintenance during 6 months. At last follow-up (7 months) he showed a persistent control of the lymphocytosis with no side effect.- - - - - - - - - - ranking = 4.7819012900968keywords = breakage (Clic here for more details about this article) |
8/68. Genetic study of a new X-linked recessive immunodeficiency syndrome.Seven forms of X-linked (XL) immunodeficiency have been described (XL agammaglobulinemia, XL severe combined immunodeficiency [SCID], wiskott-aldrich syndrome, XL chronic granulomatous disease, XL hyper-IgM syndrome with low IgG and IgA, and XL lymphoproliferative syndrome), and properdine deficiency. Although there are (some) phenotypic variants, diagnosis is relatively simple on the basis of clinical, immunological, and genetic characteristics. We studied a family in which several males were affected by severe infections and whose pedigree suggested recessive XL inheritance of an immunodeficiency. Immunologic and genetic studies (X inactivation patterns in females and restriction fragment length polymorphism [RFLP] segregation) were performed in order to characterize the immunodeficiency. The propositus, a 5-yr-old boy, was found to have a severe and progressive T- and B-cell functional immunodeficiency characterized by defective antigen-specific responses. No lymphocyte subsets or membrane anomalies were detected and the immunodeficiency did not correspond to usual XL forms. Studies of dna from two of the informative females, the mother and one sister revealed nonrandom x chromosome inactivation of T cells and, partially, B cells but not PMN, a pattern similar to that observed in XL SCID carriers. RFLP studies identified a haplotype segregating with the abnormal locus that may be localized in the proximal part of the long arm of the X chromosome. We thus report the characterization of a new XL immunodeficiency that may correspond either to another XL locus or to an attenuated phenotype of XL SCID.- - - - - - - - - - ranking = 0.087239483961279keywords = chromosome (Clic here for more details about this article) |
9/68. Rationale and results of in utero transplants of stem cells in humans.Following 18 years experience in postnatal fetal liver transplantation (FLT), we have developed a new therapeutical method, namely the in utero transplantation of stem cells from the human fetal liver. This early transplant takes advantage of the immunological tolerance that exists in young fetal recipients. The four fetuses that we treated were 28, 26, 17 and 12 weeks of age (weeks after fecundation). The first two patients had immunodeficiencies, the two other had thalassemia major. Donor cells were obtained from 7- to 12-week-old fetuses, with conditions approved by the National Committee for bioethics. Donors and recipients were not matched. The fetal cells were infused through the umbilical vein of three patients and injected intraperitoneally into the other one, under ultrasonic visualization. The first patient, bone in 1988, has evidence of engraftment and reconstitution of cell-mediated immunity: initially 10% then 26% of lymphocytes of donor origin (with distinct phenotype), T cell responses to tetanus toxoid and candida antigens. This child, who had bare lymphocyte syndrome, has no clinical manifestation of the disease and lives normally at home. The second child was born in 1989; donor cell engraftment has been proven (y chromosome in this female patient) and immunological reconstitution is in progress, allowing a normal life at home. The third patient has also evidence of donor cell take (y chromosome in a female patient) and a partial effect on thalassemia has been documented (donor haemoglobin present in small quantity). In all three cases, no side effect of any kind developed in the mother nor in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)- - - - - - - - - - ranking = 0.087239483961279keywords = chromosome (Clic here for more details about this article) |
10/68. Dermatologic and immunologic findings in the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome.BACKGROUND: The immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare genodermatosis associated with dermatitis, enteropathy, type 1 diabetes, thyroiditis, hemolytic anemia, and thrombocytopenia. IPEX results from mutations of FOXP3, a gene located on the X chromosome that encodes a dna-binding protein required for development of regulatory T cells. If untreated, affected males die early in life from malabsorption and other complications. To our knowledge, this syndrome has never been described in the dermatology literature. OBSERVATIONS: We studied an 11-year-old boy with IPEX. mutation analysis revealed a G-->A transition (1150G>A) in exon 11, resulting in a putative substitution of Ala-->Thr at residue 384, within the dna-binding site. Histopathologic examination of an active skin lesion revealed psoriasiform dermatitis. The lesions improved with clobetasol ointment. The patient also displayed alopecia universalis, which had been present since age 18 months, accompanied by longitudinal ridging of the nails. Lymphocyte challenge tests revealed a profound inability to synthesize interferon gamma (INF-gamma) and dysregulated production of other cytokines. CONCLUSIONS: IPEX is an often fatal genodermatosis associated with multiple autoimmune disorders. Cutaneous findings may include dermatitis, bullae, urticaria, alopecia universalis, and trachyonychia. Recognition of this life-threatening disorder is crucial for optimal treatment and genetic counseling.- - - - - - - - - - ranking = 0.043619741980639keywords = chromosome (Clic here for more details about this article) |
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