13 results on '"DIGEORGE syndrome"'
Search Results
2. New DiGeorge Syndrome Study Findings Have Been Reported from Department of Health of Moscow (Prognostic changes in lymphocyte subpopulations during the development of autoimmune complications in patients with DiGeorge syndrome).
- Abstract
A recent study conducted by the Department of Health of Moscow focused on patients with DiGeorge syndrome, a genetic condition characterized by immunodeficiency. The study aimed to compare the subpopulations of T and B lymphocytes in patients with and without autoimmune complications and identify prognostic signs that precede the development of complications. The researchers found that patients with autoimmune complications had a decrease in certain subpopulations of T and B lymphocytes, such as CD45RA+ naive T cells and memory B cells. These findings suggest that regular immunophenotyping, particularly of these subpopulations, can help predict autoimmune complications in patients with DiGeorge syndrome. [Extracted from the article]
- Published
- 2024
3. Neutrophils to lymphocytes ratio and psychosis in 22q11.2 deletion syndrome - Clinical and scientific implications.
- Author
-
Mekori-Domachevsky, Ehud, Taler, Michal, Weinberger, Ronnie, Guri, Yael, Dar, Shira, Shani, Shachar, Dekel, Idit, Weizman, Abraham, and Gothelf, Doron
- Subjects
- *
22Q11 deletion syndrome , *IMMUNOLOGIC diseases , *LYMPHOCYTES , *NEUTROPHILS , *PSYCHOSES , *SYMPTOMS , *DIGEORGE syndrome , *RESEARCH , *CROSS-sectional method , *RESEARCH methodology , *MEDICAL cooperation , *EVALUATION research , *COMPARATIVE studies , *DISEASE complications - Abstract
Background: Individuals with 22q11.2 deletion syndrome (22q11.2DS) are at risk for having both psychotic and immune disorders, thus, implying a possible link between the two. The aim of the current study was to evaluate the usefulness of the neutrophiles to leukocytes ratio (NLR), an inflammatory marker, as a bio-marker for overt and prodromal psychotic symptoms in 22q11.2DS.Methods: Forty-nine individuals with 22q11.2DS (13 with psychotic disorders and 36 without psychotic disorders) and 30 age- and sex-matched healthy controls underwent psychiatric evaluation using a structured psychiatric interview, the Scale of Prodromal Symptoms (SOPS) and the Global Assessment of Functioning (GAF) scale. Blood samples were collected from all participants on the day of assessment. NLR was calculated, compared among the study groups and correlated with SOPS and GAF scores. The non-psychotic 22q11.2DS group was further divided into high- and low-inflammation groups by NLR values and the analyses were done again.Results: NLR was higher in the psychotic- and the high-inflammation non-psychotic 22q11.2DS groups compared to the low-inflammation non-psychotic 22q11.2DS group and controls. In the high-inflammation non-psychotic 22q11.2DS group NLR increase was associated with an increase of total negative symptoms scores on SOPS and a decrease in GAF scores.Conclusion: Our results suggest the potential utility of NLR as a bio-marker for psychotic disorders and subthreshold prodromal symptoms in 22q11.2DS. Furthermore, they imply that a disequilibrium between the innate and adaptive arms of the immune system facilitates the progression of psychosis in at risk populations. Further longitudinal studies are warranted to validate our findings, as this was a cross sectional observation. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
4. The TREC/KREC Assay for the Diagnosis and Monitoring of Patients with DiGeorge Syndrome.
- Author
-
Froňková, Eva, Klocperk, Adam, Svatoň, Michael, Nováková, Michaela, Kotrová, Michaela, Kayserová, Jana, Kalina, Tomáš, Keslová, Petra, Votava, Felix, Vinohradská, Hana, Freiberger, Tomáš, Mejstříková, Ester, Trka, Jan, and Šedivá, Anna
- Subjects
- *
DIGEORGE syndrome , *THYMOL , *LYMPHOCYTES , *T cells , *IMMUNOLOGICAL deficiency syndromes , *BLOOD cells , *DIAGNOSIS - Abstract
: DiGeorge syndrome (DGS) presents with a wide spectrum of thymic pathologies. Nationwide neonatal screening programs of lymphocyte production using T-cell recombination excision circles (TREC) have repeatedly identified patients with DGS. We tested what proportion of DGS patients could be identified at birth by combined TREC and kappa-deleting element recombination circle (KREC) screening. Furthermore, we followed TREC/KREC levels in peripheral blood (PB) to monitor postnatal changes in lymphocyte production. Methods: TREC/KREC copies were assessed by quantitative PCR (qPCR) and were related to the albumin control gene in dry blood spots (DBSs) from control (n = 56), severe immunodeficiency syndrome (SCID, n = 10) and DGS (n = 13) newborns. PB was evaluated in DGS children (n = 32), in diagnostic samples from SCID babies (n = 5) and in 91 controls. Results: All but one DGS patient had TREC levels in the normal range at birth, albeit quantitative TREC values were significantly lower in the DGS cohort. One patient had slightly reduced KREC at birth. Postnatal DGS samples revealed reduced TREC numbers in 5 of 32 (16%) patients, whereas KREC copy numbers were similar to controls. Both TREC and KREC levels showed a more pronounced decrease with age in DGS patients than in controls (p<0.0001 for both in a linear model). DGS patients had higher percentages of NK cells at the expense of T cells (p<0.0001). The patients with reduced TREC levels had repeated infections in infancy and developed allergy and/or autoimmunity, but they were not strikingly different from other patients. In 12 DGS patients with paired DBS and blood samples, the TREC/KREC levels were mostly stable or increased and showed similar kinetics in respective patients. Conclusions: The combined TREC/KREC approach with correction via control gene identified 1 of 13 (8%) of DiGeorge syndrome patients at birth in our cohort. The majority of patients had TREC/KREC levels in the normal range. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
5. Newborn screening for primary immunodeficiencies: beyond SCID and XLA.
- Author
-
Borte, Stephan, Wang, Ning, Óskarsdóttir, Sólveig, von Döbeln, Ulrika, and Hammarström, Lennart
- Subjects
- *
IMMUNODEFICIENCY , *MEDICAL screening , *PHAGOCYTES , *SEVERITY of illness index , *AGAMMAGLOBULINEMIA , *X chromosome abnormalities , *LYMPHOCYTES ,DIAGNOSIS of neonatal diseases - Abstract
Primary immunodeficiencies (PID) encompass more than 250 disease entities, including phagocytic disorders, complement deficiencies, T cell defects, and antibody deficiencies. While differing in clinical severity, early diagnosis and treatment is of considerable importance for all forms of PID to prevent organ damage and life-threatening infections. During the past few years, neonatal screening assays have been developed to detect diseases hallmarked by the absence of T or B lymphocytes, classically seen in severe combined immunodeficiencies (SCID) and X-linked agammaglobulinemia (XLA). As described in this review, a reduction or lack of T and B cells in newborns is also frequently found in several other forms of PID, requiring supplemental investigation and involving the development of additional technical platforms in order to help classify abnormal screening results. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
6. Low thymic output in the 22q11.2 deletion syndrome measured by CCR9+CD45RA+ T cell counts and T cell receptor rearrangement excision circles.
- Author
-
Lima, K., Abrahamsen, T. G., Foelling, I., Natvig, S., Ryder, L. P., and Olaussen, R. W.
- Subjects
- *
IMMUNE system , *T cells , *LYMPHOCYTES , *CELL membranes , *LYMPHOID tissue - Abstract
Thymic hypoplasia is a frequent feature of the 22q11.2 deletion syndrome, but we know little about patients' age-related thymic output and long-term consequences for their immune system. We measured the expression of T cell receptor rearrangement excision circles (TREC) and used flow cytometry for direct subtyping of recent thymic emigrant (RTE)-related T cells in 43 patients (aged 1–54 years; median 9 years) from all over Norway and in age-matched healthy controls. Thymic volumes were estimated by ultrasound in patients. TREC levels correlated well with RTE-related T cells defined by co-expression of CD3, CD45RA and CCR9 ( r = 0·84) as well as with the CD4+ and CD8+ T cell subtypes. RTE-related T cell counts also paralleled age-related TREC reductions. CD45RA+ T cells correlated well with absolute counts of CD4+ ( r = 0·87) and CD8+ ( r = 0·75) RTE-related T cells. Apart from CD45RA- T cells, all T cell subsets were lower in patients than in controls. Thymic volumes correlated better with RTE-related cells ( r = 0·46) than with TREC levels ( r = 0·38). RTE-related T cells and TREC levels also correlated well ( r = 0·88) in patients without an identifiable thymus. Production of RTEs is impaired in patients with a 22q11.2 deletion, and CCR9 appears to be a good marker for RTE-related T cells. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
7. Persistent low thymic activity and non-cardiac mortality in children with chromosome 22q11·2 microdeletion and partial DiGeorge syndrome.
- Author
-
Eberle, P., Berger, C., Junge, S., Dougoud, S., Büchel, E. Valsangiacomo, Riegel, M., Schinzel, A., Seger, R., and Güngör, T.
- Subjects
- *
LYMPHOCYTES , *T cells , *CELL adhesion molecules , *LEUCOCYTES , *DEATH - Abstract
A subgroup of patients with 22q11·2 microdeletion and partial DiGeorge syndrome (pDGS) appears to be susceptible to non-cardiac mortality (NCM) despite sufficient overall CD4+ T cells. To detect these patients, 20 newborns with 22q11·2 microdeletion and congenital heart disease were followed prospectively for 6 years. Besides detailed clinical assessment, longitudinal monitoring of naive CD4+ and cytotoxic CD3+CD8+ T cells (CTL) was performed. To monitor thymic activity, we analysed naive platelet endothelial cell adhesion molecule-1 (CD31+) expressing CD45RA+RO-CD4+ cells containing high numbers of T cell receptor excision circle (TREC)-bearing lymphocytes and compared them with normal values of healthy children ( n = 75). Comparing two age periods, low overall CD4+ and naive CD4+ T cell numbers were observed in 65%/75%, respectively, of patients in period A (< 1 year) declining to 22%/50%, respectively, of patients in period B (> 1/< 7 years). The percentage of patients with low CTLs (< P10) remained robust until school age (period A: 60%; period B: 50%). Low numbers of CTLs were associated with abnormally low naive CD45RA+RO-CD4+ T cells. A high-risk (HR) group ( n = 11) and a standard-risk (SR) ( n = 9) group were identified. HR patients were characterized by low numbers of both naive CD4+ and CTLs and were prone to lethal infectious and lymphoproliferative complications (NCM: four of 11; cardiac mortality: one of 11) while SR patients were not (NCM: none of nine; cardiac mortality: two of nine). Naive CD31+CD45RA+RO-CD4+, naive CD45RA+RO-CD4+ T cells as well as TRECs/106 mononuclear cells were abnormally low in HR and normal in SR patients. Longitudinal monitoring of naive CD4+ and cytotoxic T cells may help to discriminate pDGS patients at increased risk for NCM. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
8. Maturational alterations of peripheral T cell subsets and cytokine gene expression in 22q11.2 deletion syndrome.
- Author
-
Kanaya, Y., Ohga, S., Ikeda, K., Furuno, K., Ohno, T., Takada, H., Kinukawa, N., and Hara, T.
- Subjects
- *
CYTOKINES , *CARDIOVASCULAR diseases , *LYMPHOCYTES , *T cells , *HYPOCALCEMIA - Abstract
Chromosome 22q11.2 deletion syndrome is a common disorder characterized by thymic hypoplasia, conotruncal cardiac defect and hypoparathyroidism. Patients have a risk of infections and autoimmunity associated with T lymphocytopenia. To assess the immunological constitution of patients, the numerical changes and cytokine profile of circulating T cells were analysed by flow cytometry and real-time polymerase chain reaction (PCR). CD3+, CD4+, T cell receptor (TCR)αβ+ or CD8αα+ cell counts were lower, and CD56+ cell counts were higher in patients than in controls during the period from birth to adulthood. The ageing decline of CD3+ or CD4+ cell counts was slower in patients than in controls. The proportion of CD8αα+ cells increased in controls, and the slope index was larger than in patients. On the other hand, both the number and proportion of Vα24+ cells increased in patients, and the slope indexes tended to be larger than in controls. The positive correlation of the number of T cells with CD8αα+ cells was observed only in patients, and that with Vα24+ cells was seen only in controls. No gene expression levels of interferon (IFN)-γ, interleukin (IL)-10, transforming growth factor (TGF)-β, cytotoxic T lymphocyte antigen 4 (CTLA4) or forkhead box p3 (Foxp3) in T cells differed between patients and controls. There was no significant association between the lymphocyte subsets or gene expression levels and clinical phenotype including the types of cardiac disease, hypocalcaemia and frequency of infection. These results indicated that T-lymphocytopenia in 22q11.2 deletion patients became less severe with age under the altered composition of minor subsets. The balanced cytokine profile in the limited T cell pool may represent a T cell homeostasis in thymic deficiency syndrome. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
9. Risk factors of clinical dysimmune manifestations in a cohort of 86 children with 22q11.2 deletion syndrome: A retrospective study in France
- Author
-
Pierre Portales, Pierre Sarda, Marie-José Perez, Gregory Marin, Claire Lozano, Eric Jeziorski, Nicolas Nagot, Pascal Amedro, Perrine Mahe, Thierry Vincent, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), MORNET, Dominique, and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
- Subjects
0301 basic medicine ,Male ,lymphocytes ,Allergy ,030105 genetics & heredity ,medicine.disease_cause ,Severity of Illness Index ,Autoimmunity ,T-Lymphocyte Subsets ,Prevalence ,infections ,Child ,Genetics (clinical) ,autoimmunity ,3. Good health ,Immunoglobulin Isotypes ,Phenotype ,Child, Preschool ,Cohort ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,Disease Susceptibility ,France ,medicine.medical_specialty ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics ,Autoimmune Diseases ,03 medical and health sciences ,22q11 Deletion Syndrome ,[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics ,Internal medicine ,Genetics ,medicine ,DiGeorge Syndrome ,Hypersensitivity ,Humans ,Risk factor ,Autoimmune disease ,22q11 deletion syndrome ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,business.industry ,dysimmunity ,Infant ,Retrospective cohort study ,medicine.disease ,Confidence interval ,030104 developmental biology ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business - Abstract
International audience; In this study, we describe the biological immune profiles and clinical dysimmune manifestations (infections, autoimmune diseases, and allergies) of patients with 22q11.2 deletion syndrome with the aim of determining risk factors for clinical events. This retrospective study concerned all the patients with 22q11 deletion syndrome attending the Montpellier University Hospital from January 1, 1992, to December 31, 2014 who had at least one immune investigation before the age of 18. We analyzed the clinical features, biological tests and the course of infections, autoimmunity, and allergy of 86 children. Among these 86 children, 48 (59%) had a low T lymphocyte level. Twenty-nine patients (34%) had a severe infection. The only risk factor for severe infection was the low level of CD4+ T-cells (OR: 3.3; 95% confidence interval (CI) [1.020-11.108]). Eleven patients (13%) developed an autoimmune disease; the only risk factor was an antecedent of severe infection (OR: 4.1; 95% CI [1.099-15.573]). Twenty-three patients (27%) had allergic episodes. A low level of CD8+ T-cells (OR: 3.2; 95% CI [1.07-9.409]) was significantly associated with allergy manifestations. Patients with 22q11 deletion syndrome have a high rate of dysimmune manifestations. We found statistic correlations among CD4+ T-cell count, infectious manifestations, and autoimmunity.
- Published
- 2019
10. Increased spontaneous apoptosis in T lymphocytes in DiGeorge anomaly.
- Author
-
Gupta, S., Aggarwal, S., and Nguyen, T.
- Subjects
- *
APOPTOSIS , *LYMPHOCYTES , *T cells , *BLOOD - Abstract
The aim of this study was to determine whether increased apoptosis in peripheral blood lymphocytes plays a role in T cell deficiency associated with DiGeorge anomaly. T cell subsets from a patient with DiGeorge anomaly were examined for the expression of Fas, FasL, Bcl-2 and Bcl-XL at the protein level with monoclonal antibodies, using dual-colour flow cytometry, and at the mRNA level in mononuclear cells by quantitative reverse transcriptase-polymerase chain reaction. In vitro spontaneous apoptosis was examined by propidium iodide staining and DNA fragmentation, using flow cytometry and gel electrophoresis, respectively. Fas and FasL expression, both at the level of protein and of mRNA, was increased, whereas Bcl-2 expression was decreased both at the level of protein and of mRNA. However, no difference in Bcl-XL expression was observed between the patient and an age-matched control. A significant proportion of both CD4+ and CD8+ T cells from the patients underwent spontaneous apoptosis, whereas almost no spontaneous apoptosis was observed in the age-matched control. These data suggest that spontaneous apoptosis in T lymphocytes, at least in part, may be responsible for T cell deficiency in DiGeorge anomaly. [ABSTRACT FROM AUTHOR]
- Published
- 1998
- Full Text
- View/download PDF
11. The TREC/KREC Assay for the Diagnosis and Monitoring of Patients with DiGeorge Syndrome
- Author
-
Jana Kayserova, Petra Keslova, Hana Vinohradská, Tomáš Freiberger, Michaela Kotrova, Felix Votava, Adam Klocperk, Tomas Kalina, Ester Mejstříková, Michael Svatoň, Eva Froňková, Michaela Novakova, Anna Sediva, and Jan Trka
- Subjects
Male ,B Cells ,T-Lymphocytes ,lcsh:Medicine ,Gastroenterology ,White Blood Cells ,Animal Cells ,DiGeorge syndrome ,Genetics of the Immune System ,Medicine ,Lymphocytes ,lcsh:Science ,Child ,Immunodeficiency ,Cells, Cultured ,Multidisciplinary ,T Cells ,3. Good health ,Child, Preschool ,Cohort ,Biological Assay ,Female ,Cellular Types ,DNA, Circular ,Research Article ,medicine.medical_specialty ,Adolescent ,Immune Cells ,Immunology ,Real-Time Polymerase Chain Reaction ,Immune Deficiency ,Neonatal Screening ,Internal medicine ,DiGeorge Syndrome ,Humans ,Normal range ,Severe combined immunodeficiency ,Blood Cells ,business.industry ,lcsh:R ,Immunologic Deficiency Syndromes ,Infant, Newborn ,Biology and Life Sciences ,Infant ,Cell Biology ,medicine.disease ,Minimal residual disease ,Peripheral blood ,Transplantation ,lcsh:Q ,Clinical Immunology ,Severe Combined Immunodeficiency ,business - Abstract
DiGeorge syndrome (DGS) presents with a wide spectrum of thymic pathologies. Nationwide neonatal screening programs of lymphocyte production using T-cell recombination excision circles (TREC) have repeatedly identified patients with DGS. We tested what proportion of DGS patients could be identified at birth by combined TREC and kappa-deleting element recombination circle (KREC) screening. Furthermore, we followed TREC/KREC levels in peripheral blood (PB) to monitor postnatal changes in lymphocyte production. Methods TREC/KREC copies were assessed by quantitative PCR (qPCR) and were related to the albumin control gene in dry blood spots (DBSs) from control (n = 56), severe immunodeficiency syndrome (SCID, n = 10) and DGS (n = 13) newborns. PB was evaluated in DGS children (n = 32), in diagnostic samples from SCID babies (n = 5) and in 91 controls. Results All but one DGS patient had TREC levels in the normal range at birth, albeit quantitative TREC values were significantly lower in the DGS cohort. One patient had slightly reduced KREC at birth. Postnatal DGS samples revealed reduced TREC numbers in 5 of 32 (16%) patients, whereas KREC copy numbers were similar to controls. Both TREC and KREC levels showed a more pronounced decrease with age in DGS patients than in controls (p
- Published
- 2014
12. The ontogeny of human lymphocyte recirculation: high endothelial cell antigen (HECA-452) and CD44 homing receptor expression in the development of the immune system
- Author
-
Chris J.L.M. Meijer, N. Hartwig, Adrian M. Duijvestijn, Steven T. Pals, H. J. van der Harten, E. Horst, and Other departments
- Subjects
Lymphoid Tissue ,Receptor expression ,Lymphocyte ,Immunology ,High endothelial venules ,Palatine Tonsil ,Receptors, Lymphocyte Homing ,Gestational Age ,Thymus Gland ,Biology ,Antigen ,Antigens, CD ,Cell Movement ,medicine ,DiGeorge Syndrome ,Immunology and Allergy ,Humans ,Endothelium ,Lymphocytes ,Lymphocyte homing receptor ,CD44 ,Infant, Newborn ,Germinal center ,Antibodies, Monoclonal ,Antigens, Differentiation ,medicine.anatomical_structure ,Lymphatic system ,Antigens, Surface ,biology.protein ,Lymph Nodes ,Endothelium, Lymphatic - Abstract
In the present report we have studied the expression of a lymphocyte homing receptor, the CD44 antigen, and of HECA-452, a high endothelial-specific antigen, during the development of the human immune system. We found that prothymocyte immigrants of the thymus already expressed the CD44 antigen. Similarly, the first peripheral T lymphocytes in fetal lymph nodes, tonsils and gut-associated lymphoid tissue were also CD44+. Cortical thymocytes and germinal center cells were CD44-. CD44 antigen expression was, thus, not limited to mature recirculating lymphocytes. This suggests that CD44 may not only be involved in recirculation of mature lymphocytes but also in the migration of prothymocytes to their site of maturation, i.e. the thymus. High endothelial venules (HEV) were not demonstrable at the early onset of lymphocyte immigration into the developing lymphoid organs. However, when large-scale influx of lymphocytes occurred, it paralleled HEV development. HECA-452 antigen expression preceded the morphological transformation of endothelium into a HEV phenotype. Expression of this antigen therefore, independently reflected the specialized nature of high endothelium. In a patient with complete DiGeorge's syndrome normal HEV developed, indicating that the presence of T lymphocytes is not a requirement for HEV development. Interestingly, a subpopulation of venules located in the thymic medulla near the cortico-medullary junction expressed the HECA-452 antigen. These vessels, which had flat or intermediately high endothelium, are probably involved in lymphocyte migration to the thymus.
- Published
- 1990
13. Altered replication timing of the HIRA/Tuple1 locus in the DiGeorge and Velocardiofacial syndromes
- Author
-
Patrizia Di Mare, Simona D'Antoni, Teresa Mattina, Salvatore Motta, Concetta Federico, and Salvatore Saccone
- Subjects
Adult ,DNA Replication ,Heart Defects, Congenital ,Male ,Candidate gene ,DNA Replication Timing ,Hypoparathyroidism ,Chromosomes, Human, Pair 22 ,Locus (genetics) ,Cell Cycle Proteins ,Biology ,HIRA/Tuple1 ,Human chromosome 22 ,Craniofacial Abnormalities ,DiGeorge syndrome ,Genetics ,medicine ,DiGeorge Syndrome ,Humans ,Abnormalities, Multiple ,Histone Chaperones ,Lymphocytes ,Interphase nuclei ,Child ,In Situ Hybridization, Fluorescence ,Position effect ,Regulation of gene expression ,Cell Nucleus ,Replication timing ,Cell Cycle ,DNA replication ,Infant ,Deletion syndrome ,General Medicine ,Syndrome ,medicine.disease ,Child, Preschool ,Female ,Chromosome Deletion ,Haploinsufficiency ,Transcription Factors - Abstract
DiGeorge and Velocardiofacial syndromes (DGS/VCFS) are endowed by a similar complex phenotype including cardiovascular, craniofacial, and thymic malformations, and are associated with heterozygous deletions of 22q11 chromosomal band. The Typically Deleted Region in the 22q11.21 subband (here called TDR22) is very gene-dense, and the extent of the deletion has been defined precisely in several studies. However, to date there is no evidence for a mechanism of haploinsufficiency that can fully explain the DGS/VCFS phenotype. In this study, we show that the candidate gene HIRA/Tuple1 mapping on the non-deleted TDR22, in DGS/VCFS subjects presents a delayed replication timing. Moreover, we observed an increase in the cell ratio showing the HIRA/Tuple1 locus localised toward the nuclear periphery. It is known that replication timing and nuclear location are generally correlated to the transcription activity of the relative DNA region. We propose that the alteration in the replication/nuclear location pattern of the non-deleted TDR22 indicates an altered gene regulation hence an altered transcritpion in DGS/VCFS. © 2004 Elsevier B.V. All rights reserved.
- Published
- 2004
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.