1/30. Possible extrathymic development of nonfunctional T cells in a patient with complete digeorge syndrome.Complete digeorge syndrome is characterized by the clinical triad of cardiac malformation, hypocalcemia, and T cell immunodeficiency due to congenital athymia. We describe an infant with complete digeorge syndrome who at presentation had no circulating T cells detectable by flow cytometry. The patient spontaneously developed circulating T cells but these cells did not proliferate in response to mitogens. The T cell receptor Vbeta repertoire was severely restricted. All T cells were host, not maternal, as assessed by fluorescent in situ hybridization evaluation of 22q11 hemizygosity. At autopsy, this patient had no grossly detectable thymus tissue and no microscopic evidence for thymopoiesis. These findings suggest that appearance of T cells in infants with complete digeorge syndrome may represent oligoclonal expansions of a small number of T cells that may have matured extrathymically and which do not respond in vitro to mitogen stimulation.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/30. Patient with a 22q11.2 deletion with no overlap of the minimal digeorge syndrome critical region (MDGCR).The apparent lack of genotype/phenotype correlation in patients with the DiGeorge anomaly and velocardiofacial syndrome (DGA/VCFS; the "22q11 deletion syndrome") indicates a complex genetic condition. Most cases, whatever the phenotype, have a 1.5-3 Mb chromosomal deletion that includes the minimal DiGeorge critical region (MDGCR). Another potential critical region on 22q11 has been suggested based on two patients with distal deletions outside the MDGCR. We report on a patient with a VCFS phenotype who has a deletion, mapped by short tandem repeat polymorphic loci and fluorescence in situ hybridization analysis, distal to and not overlapping the MDGCR. This patient is deleted for several genes, including the T-box 1 gene (TBX1; a transcription regulator expressed early in embryogenesis) and catechol-O-methyltransferase (COMT; involved in neurotransmitter metabolism). We discuss the role these two genes may play in the clinical phenotype of the patient.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/30. Interruption of the aortic arch at the isthmus with digeorge syndrome and 22q11.2 deletion.A 6-day-old male with interruption of the aortic arch at the isthmus (type A) had the typical phenotype of digeorge syndrome. There was also a doubly committed juxta-arterial ventricular septal defect and an unobstructed left ventricular outflow tract. Hypoplasia of the thymus was confirmed during a modified Blalock-Park operation. He had persistent hypocalcemia, and was susceptible to infection. He was subsequently revealed by the use of fluorescence in situ hybridization analysis to have 22q11.2 deletion. Interruption of the aortic arch at the isthmus is presumed to reflect abnormal fetal hemodynamics, and is considered a distinct pathogenetic entity from interruption between the left common carotid and subclavian arteries, the latter being the variant more frequently associated with digeorge syndrome. In our case, the 22q11.2 deletion likely played a major role in the etiology of the interrupted aortic arch.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/30. Dual-probe fluorescence in situ hybridization assay for detecting deletions associated with VCFS/digeorge syndrome I and digeorge syndrome II loci.Over 90% of patients with digeorge syndrome (DGS) or velocardiofacial syndrome (VCFS) have a microdeletion at 22q11.2. Given that these deletions are difficult to visualize at the light microscopic level, fluorescence in situ hybridization (FISH) has been instrumental in the diagnosis of this disorder. Deletions on the short arm of chromosome 10 are also associated with a DGS-like phenotype. Since deletions at 22q11.2 and at 10p13p14 result in similar findings, we have developed a dual-probe FISH assay for screening samples referred for DGS or VCFS in the clinical laboratory. This assay includes two test probes for the loci, DGSI at 22q11.2 and DGSII at 10p13p14, and centromeric probes for chromosomes 10 and 22. Of 412 patients tested, 54 were found to be deleted for the DGSI locus on chromosome 22 (13%), and a single patient was found deleted for the DGSII locus on chromosome 10 (0. 24%). The patient with the 10p deletion had facial features consistent with VCFS, plus sensorineural hearing loss, and renal anomalies. cytogenetic analysis showed a large deletion of 10p [46, XX,del(10)(p12.2p14)] and FISH using a 10p telomere region-specific probe confirmed the interstitial nature of the deletion. Analysis for the DGSI and the DGSII loci suggests that the deletion of the DGSII locus on chromosome 10 may be 50 times less frequent than the deletion of DGSI on chromosome 22. The incidence of deletions at 22q11.2 has been estimated to be 1 in 4000 newborns; therefore, the deletion at 10p13p14 may be estimated to occur in 1 in 200,000 live births.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
5/30. Simultaneous multiorgan presence of human herpesvirus 8 and restricted lymphotropism of Epstein-Barr virus dna sequences in a human immunodeficiency virus-negative immunodeficient infant.Because a profound dysregulation of the immune system occurs in primary immunodeficiencies, viral infections are not uncommon. Human herpesvirus (HHV)-8 dna was detected by polymerase chain reaction (PCR) analysis, Southern blotting, and in situ hybridization (ISH) in peripheral blood mononuclear cells and lymphoid organs (bone marrow, spleen, and lymph nodes) and endothelial and epithelial cells and macrophages from several organs (skin, lung, esophagus, intestine, choroid plexus [but not in brain or cerebellum], heart, striated muscle, liver, and kidney) of a human immunodeficiency virus-negative infant with DiGeorge anomaly who died of disseminated infection. Epstein-Barr virus dna sequences were detected in the spleen and lymph nodes (by PCR and ISH) and in bone marrow (only by ISH) but not in blood or nonlymphoid organs. This report is believed to be the first of multiorgan dissemination of HHV-8 in a primary immunodeficiency.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/30. Neurological presentation of three patients with 22q11 deletion (CATCH 22 syndrome).Chromosome 22q11 deletion (CATCH 22 syndrome or velocardiofacial syndrome) is one of the most frequent chromosomal syndromes. Neurological features other than cognitive disorders are probably the least-described part of the expanding phenotype of the 22q11 deletion. We report the neurological features of three unrelated children with a de novo deletion: one patient with an autistic disorder, a second patient with hypocalcaemic neonatal seizures and unusual persistent epileptic focus at electroencephalographic follow-up, and a third patient with atypical absence epilepsy. These observations enlarge the clinical and neurological spectrum of the 22q11 deletion. awareness of such cases is necessary, and a diagnosis of the 22q11 deletion should be suspected in children with common neurological features associated with severe or mild dysmorphism. diagnosis of the 22q11 deletion should be confirmed by fluorescence in situ hybridization analysis associated with standard chromosomal analysis.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
7/30. Molecular cytogenetic characterization of a 10p14 deletion that includes the DGS2 region in a patient with multiple anomalies.We report on a prenatally diagnosed four-month-old boy with DiGeorge-like phenotype and a deletion of chromosome 10pter --> 14. fluorescence in situ hybridization (FISH) experiments using phage artificial chromosome (PAC) and yeast artificial chromosome (YAC) clones indicated that the chromosomal breakpoint was located at the proximal boundary of the digeorge syndrome 2 (DGS2) critical region. The patient demonstrated a high forehead, high arched eyebrows, short palpebral fissures, sparse eyelashes, prominent nose with bulbous tip, small mouth, receding chin, round ears with deficient helices, cardiac defects atrial septal defect (ASD), ventricular septal defect (VSD), mild brachytelephalangy, mild syndactyly, hypoplastic left kidney, undescended testes, muscular hypertonia, dorsally flexed big toes, and developmental delay. The phenotype corresponded well with the clinical signs of 10p deletion of this region that were described previously. The facial features appeared different from the typical face with the 22q11 deletion.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
8/30. DiGeorge/velocardiofacial syndrome: FISH studies of chromosomes 22q11 and 10p14, and clinical reports on the proximal 22q11 deletion.DiGeorge anomaly/velocardiofacial syndrome (DG/VCFS) occurs with different deletion intervals on chromosomes 22q11, while the DiGeorge anomaly (with other findings) is seen in patients with deletions of 10p14. The clinical outcome with the common 22q11 deletion (90% of cases) is well known, but the outcome with the less frequent deletion types has not been well documented. Using cytogenetic and fluorescence in situ hybridization (FISH) analysis we studied a series of 295 patients with suspected DG/VCFS. We identified 58 subjects with a 22q11 deletion, and none with a 10p deletion. Fifty-two subjects had the common deletion, five had the proximal deletion, and one had an atypical proximal deletion due to a 1;22 translocation. We report clinical data of four subjects with the proximal 22q11 microdeletion, and of one patient with the atypical proximal deletion. The anomalies observed with the proximal 22q11 microdeletion fell within the DG/VCFS spectrum. Two females, 6 and 25 years old, had normal mental development. Normal development has been reported with the common 22q11 deletion, but only in a minority of cases. This study may indicate a better intellectual and/or behavioral outcome with the proximal vs. the common 22q11 deletion, rather than a chance finding.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
9/30. Does chromosome 22 have anything to do with sex determination: further studies on a 46,XX,22q11.2 del male.Several years ago, we presented a patient with true hermaphroditism and partial duplication of chromosome 22 and no evidence of SRY (Aleck et al. [1999: Am J Med Genet 85:2-4]). Recently a 46,XX male with velocardiofacial syndrome and a deletion of 22q11.2 and no evidence of Y chromosomal loci in blood dna was reported (Phelan et al. [2003: Am J Med Genet 116A:77-79]). We have restudied this patient as he enters puberty. Because chromosomal deletions sometimes involve micro rearrangements of nearby material, we have extensively studied this individual's chromosome 22 looking for evidence of any gene duplication. We studied a number of variable number tandem repeat (VNTR) loci along chromosome 22 in the patient and both parents. Normal Mendelian inheritance of the VNTRs was found. We then used quantitative multiplex PCR of short fluorescent fragments (QMPSF) to delineate the 22q11.2 deletion in this patient (Jacquet et al. [2002: Hum Molec Genet 11:2243-2249]) and found a pattern of deletion typical of the velocardiofacial digeorge syndrome. Finally, the patient's dna has been analyzed using a full coverage human chromosome 22 genomic microarray (array comparative genomic hybridization [CGH]) for evidence of rearrangements outside the classical velocardiofacial DiGeorge associated deletion (Buckley et al. [2002: Hum Molec Genet 11:3221-3229]). The array-CGH profile of this patient confirms the deletion encompassing the typically deleted region associated with the velocardiofacial digeorge syndrome and provides no support for additional gene copy number aberrations on 22q. Thus, there is no evidence of any chromosome 22 trisomic material. In this case, the rare events of sex reversal and 22q11.2 deletion may have occurred together by chance.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
10/30. Molecular studies of a translocated (X;22) DiGeorge patient using somatic cell hybridization.In order to better characterize the chromosomic rearrangement of an unbalanced 45XX t(X;22) (q28;q11) DiGeorge patient, a somatic hybrid clone segregating the translocated chromosome was constructed and investigated using X and 22 linked markers. Our study demonstrated that this de novo translocation was from paternal origin. The breakpoint was assigned between DXS296 and IDS loci at Xq28 and between D22S9 and BCRL2 at 22q11. This observation and published data allow to locate a "critical region" for digeorge syndrome between these two last loci on 22q11. Our hybrid clone may be a useful tool for mapping new probes arising in this region.- - - - - - - - - - ranking = 4keywords = hybridization (Clic here for more details about this article) |
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