Disease relevance of DGCR

• The increased prevalence of schizophrenia among patients with the 22q11 interstitial deletion associated with DiGeorge syndrome has suggested the existence of a susceptibility gene for schizophrenia within the DiGeorge syndrome chromosomal region (DGCR) on 22q11 [1].
• Mice homozygous for Pax3 mutations die in utero with a phenocopy of DGS, or neonatally with neural tube defects [2].
• CATCH 22 is a medical acronym for cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, and hypocalcemia, and a variable deletion on chromosome 22q11 [3].
• Thus, at the molecular level, DGS-related breakpoints can be distinguished from the 22q11 breakpoint of CML, but not from the 8;22 translocation of Burkitt lymphoma or from the 21;22 translocations that we have previously studied [4].
• Deletions were rare among patients lacking typical DiGeorge syndrome (DGS) or velocardiofacial (VCF) dysmorphic features, and more common in tetralogy of Fallot with pulmonary atresia than tetralogy of Fallot alone [5].

Psychiatry related information on DGCR

• The patient has some features which have been reported in individuals with DGS/VCFS, including: facial dysmorphia, mental retardation, long slender digits and genital anomalies [6].
• Schizophrenia or schizoaffective disorders are often found in patients affected by DiGeorge/velo-cardio-facial syndrome (DGS/VCFS) as a result of hemizygosity of chromosome 22q11 [7].
• CONCLUSION: Oriented screening based on transfusion or drug addiction history seems to have better efficiency than the screening policy recommended by the DGS [8].
• In the second of two articles in involving mental health users in service development, Vivien Lindow discusses the Catch-22 of stigma and representativeness [9].

High impact information on DGCR

• Thus, altered stoichiometry of complexes containing HIRA may be important for the development of structures affected in WS and DGS [2].
• A number of single case reports with deletions of 10p suggest genetic heterogeneity of DGS [10].
• DiGeorge syndrome (DGS), a developmental defect, is characterized by cardiac defects and aplasia or hypoplasia of the thymus and parathyroid glands [11].
• DGS has been associated with visible chromosomal abnormalities and microdeletions of 22q11, but only one balanced translocation--ADU/VDU t(2;22)(q14;q11.21) [11].
• Transcription, apoptosis and p53: catch-22 [12].

Chemical compound and disease context of DGCR

• Seven formalin-fixed, paraffin-embedded heart specimens set up at autopsy performed from 3 to 18 years before analysis of newborns in which DiGeorge syndrome (DGS) was suspected were evaluated by fluorescence in situ hybridization (FISH) using a DGS region-specific probe and a control probe on nuclei released from thick sections [13].
• OBJECTIVE AND DESIGN: Oriented hepatitis C virus (HCV) screening on the basis of transfusion, previous or current parenteral drug addiction, invasive procedures, and in family members of patients with hepatitis C, was recommended in France by the 'Direction Générale de la Santé' (DGS) [8].

Biological context of DGCR

• We have used gene targeting in the mouse to delete a defined region within the conserved DGS critical region (DGCR) on mouse chromosome 16 to prospectively investigate the role of the mouse DGCR in 22q11 syndromes [14].
• A wide spectrum of birth defects are caused by deletions of the DiGeorge syndrome critical region (DGCR) at human chromosome 22q11 [15].
• Using probes and cosmids from the DiGeorge critical region (DGCR), deletions of 22q11 were detected in 83% of DGS and 68% of VCFS patients by DNA dosage analysis, fluorescence in situ hybridisation, or by both methods [16].
• We conclude that FISH is an efficient and direct method for the detection of 22q11 deletions in subjects with features of DGS and VCFS as well as in pregnancies at high risk for a deletion [16].
• We report the results of fluorescence in situ hybridization with cosmid probes for loci D22S75 (N25) and D22S259 (R32) within the DiGeorge chromosomal region (DGCR) on metaphase spreads from an additional 5 patients, 2 non-Japanese and 3 Japanese, with KS [17].

Anatomical context of DGCR

• Using a probe for the D22S9 locus, we have examined DNA from eight DGS cell lines and from one balanced-translocation carrier parent of a DGS proband [18].
• Although it is not a frequent finding, unilateral facial nerve palsy will be included among the symptoms of CATCH 22 syndrome [3].
• DiGeorge syndrome (DGS) is a congenital disease characterized by defects in organs and tissues that depend on contributions by cell populations derived from neural crest for proper development [19].
• Hypoplasia of the thymus hypocalcaemia, and seizures in early infancy, which are clinical features of DGS, were also observed [20].
• Because many of the tissues and structures affected in VCFS/DGS derive from the pharyngeal arches of the developing embryo, it is believed that haploinsufficiency of a gene(s) involved in embryonic development may be responsible for its etiology [21].

Associations of DGCR with chemical compounds

• The region of chromosome 22q11 responsible for the haploinsufficiency syndromes (the DiGeorge Critical Region or DGCR) has been mapped using RFLPs, quantitative Southern blotting and FISH [22].
• All results were compared with VCF, a currently marketed film containing nonoxynol-9 (N-9) [23].
• The transition from latent to overt hypoparathyroidism in a child with CATCH 22 who showed subnormal parathyroid hormone response to ethylenediaminetetraacetic acid infusion [24].
• We can partially rescue one salient feature of DGS in Crkl+/-;Tbx1+/- embryos by genetically reducing the amount of RA produced in the embryo [25].
• The sodium fluoride 'catch-22' [26].

Other interactions of DGCR

• Thus, the region critical to DGS (DGCR) may be in proximity to the BCRL2 locus [18].
• Fluorescence in situ hybridization (FISH) using the DiGeorge chromosome region (DGCR) probe (Oncor) was used to detect 31 deletions in 100 patients with possible VCFS [27].
• Using this methodology, we have mapped the human homolog of a rodent citrate transport protein to the DGCR [28].
• A critical haploinsufficiency region for DGS/VCFS was defined on 10p (DGCR2) [29].
• The DiGeorge syndrome (DGS) is a developmental defect of the third and fourth pharyngeal pouches, which is associated with congenital heart defects, hypoparathyroidism, cell-mediated immunodeficiency, velo-pharyngeal insufficiency and craniofacial dysmorphism [30].

Analytical, diagnostic and therapeutic context of DGCR

• Fluorescence in situ hybridization (FISH) studies confirmed loss of the proximal DiGeorge chromosomal region (DGCR) [31].
• 2. Fifty CTAFS patients and 10 DGA patients, 11 parents couples and 10 mothers of CTAFS patients, and 3 parents couples and 2 mothers of DGA patients were examined by fluorescent in situ hybridization (FISH) using the N25 (D22S75) DGCR probe (Oncor) [32].
• To demonstrate the efficiency, sensitivity, and specificity of PRINS in the diagnosis of microdeletions, we studied groups of patients with Prader Willi/Angelman (PWS/AS) syndrome and DiGeorge/velocardiofacial syndrome (DGS/VCFS) [33].
• We report on a prenatal diagnosis by FISH of a familial 22q11 deletion associated with DiGeorge syndrome (DGS) [34].
• We performed fluorescence in situ hybridisations (FISH) and polymerase chain reaction (PCR) analyses in 12 patients with 10p deletions, nine of them with features of DGS, and in a familial translocation 10p;14q associated with midline defects [35].

References