Francesca Crosti

Deletion of parental GST genes as a possible susceptibility factor in the etiology of infant leukemia.

Infant leukemia below the age of 12 months is a rare disease that exhibits a high frequency of 11q23 rearrangements. We assessed the presence of polymorphisms in several metabolic genes in 23 families of infants diagnosed with leukemia under 12 months of age in Italy. When polymorphism frequencies were calculated within families, frequencies of GST gene deletions were significantly higher than expected only among the parents of infants without the 11q23 rearrangement. These data suggest that the deletion of GST genes in parents may affect the risk of infant leukemia through a pathway independent of the MLL gene.

Partial duplication of the PARK2 gene in a child with developmental delay and her normal mother: A second report

Partial Duplication of the PARK2 Gene in a Child With Developmental Delay and her Normal Mother: A Second Report Milena Mariani, Francesca Crosti, Serena Redaelli, Chiara Fossati, Roberta Piras, Andrea Biondi, Leda Dalprà, and Angelo Selicorni* U.O.S. Genetica Clinica Pediatrica, Clinica Pediatrica Università Milano Bicocca, Fondazione MBBM, A.O. S. Gerardo, Monza (MB), Italy U.S. di Genetica Medica, A.O. S. Gerardo, Monza (MB), Italy Università degli Studi di Cagliari, Cagliari, Italy Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, Cittadella Universitaria di Cagliari, Monserrato (CA), Italy Clinica Pediatrica Università Milano Bicocca, Fondazione MBBM, A.O. S. Gerardo, Monza (MB), Italy

Signalling in human tumour infiltrating lymphocytes: the CD28 molecule is functional and is physically associated with the CD45R0 molecule.

The CD28 T cell activation pathway was functional in human tumour infiltrating lymphocytes (TIL) and can induce strong proliferation, lymphokine release and calcium mobilisation. Conversely, TIL responded poorly to stimulation via CD2, and CD28 did not synergise with CD2, which is at variance with that observed using peripheral lymphocytes from the same patients. On stimulation with anti-CD28 the monoclonal antibody, most TILs, which were CD3+, CD28+ and CD45R0+ at the beginning of culture, co-expressed both high (CD45RA) and low (CD45R0) molecular weight isoforms of CD45. CD28 was associated with the CD45R0 isoform at the cell surface of activated TIL, as demonstrated by immunoprecipitation and immunoenzymatic assay. Thus CD28 can substitute for CD3 in TIL leading to the expansion of functional lymphocytes and to the amplification of antitumour immune response.

Lymph node hyperplasia: clonal chromosomal and genomic rearrangements. Report of two new cases and literature review

Cytogenetic analysis is not routinely performed on lymph node hyperplasia (LH). We describe clonal chromosomal rearrangements in two unrelated cases of LH. Lymph nodes of both patients showed typical morphologic features of benign follicular hyperplasia. Cytogenetic analysis revealed clonal chromosomal rearrangements in both cases. Patient 1 showed interstitial 14q and 6q mosaic deletions, whereas patient 2 showed a terminal 14q mosaic deletion. Fluorescence in situ hybridization with IGH break-apart probes identified a partial deletion of IGH in both cases, but the loss of the LSI IGH in patient 2 and loss of the LSI IGHV in patient 1 were observed on the morphologically normal chromosome 14. In the latter case, the finding of two morphologically normal chromosomes 14 with the IGHV deletion in one of the chromosomes suggested that the first mutational event was the IGH deletion and the second event was the interstitial deletion of chromosome 14 with the IGH intact. Array comparative genomic hybridization performed on both biopsies confirmed the IGH deletion at mosaic, but not the chromosomal deletion. Patient 1 was re-biopsied after 9 months and a marginal zone lymphoma was diagnosed. The finding of clonal cytogenetic abnormalities in LH highlighted the difficulties in interpretation of results and clinical follow-up.

Impairment of lymphocyte suppressive system in recent onset insulin-dependent diabetes mellitus. correlation with blood glucose and serum insulin levels

SummaryIn a previous study, we observed an impairment of the theophylline-induced suppressive system in recent onset IDDM patients, and demonstrated also a correlation with metabolic derangement. The aim of this study was to better investigate the relationship between theophylline sensitivity (ThS) and blood glucose/plasma insulin levels in recent onset IDDM patients subjected to preprogrammed variations by an insulin/glucose clamp with artificial pancreas. Eight patients were studied within 8 weeks from the onset of IDDM. ThS was evaluated as the ability of theophylline to inhibit blastogenic response of peripheral blood lymphocytes (PBL) to Concanavalin A (ConA), after 120 min preincubation of the cells. All patients were connected to an artificial pancreas. Through i.v. continuous insulin infusion (0.02 U/kg/h) and/or i.v. continuous glucose and saline infusion, the following experimental conditions, lasting at least 1h, were obtained: T1: relative euglycemia and normal insulinemia; T2: relative euglycemia and hyperinsulinemia; T3: hyperglycemia and normal insulinemia; T4: hyperglycemia and hyperinsulinemia. ThS was maintained in 6/8 patients at T1 and in 8/8 patients at T4. ThS was lost in 4/8 patients at T2 and T3. These data suggest that the loss of ThS induced by hyperglycemia can be corrected by hyperinsulinemia, and that it is maintained when euglycemia is accompained by hypoinsulinemia. It is lost when these two parameters lose their interrelationship.

Familiar unbalanced complex rearrangements involving 13 p-arm: description of two cases

BackgroundCopy number variations (CNVs) are largely known today, but their position is rarely established by fluorescence in situ hybridization (FISH) or karyotype analysis.Case presentationWe described two families with copy number gain in which FISH analysis with the specific subtelomeric probe of chromosome 4q and 7q evidenced a third signal at band 13p11.2. Genomic study by array comparative genomic hybridization defined the triple dose segment. In the first case, the duplicate tract is free of known genes, in the second one it contained three expressed genes.ConclusionsThe CNV localization on the short arm of an acrocentric chromosome could explain the lack of phenotypic effect, being known the regulatory role of heterochromatin in the position-effect silencing. Furthermore, we would like to underline the importance of using complementary techniques such as FISH and array-CGH to obtain a better definition of genomic rearrangements.

Currarino syndrome and microcephaly due to a rare 7q36.2 microdeletion: a case report

BackgroundCurrarino syndrome is a rare condition characterized by presacral mass, anorectal malformation and sacral dysgenesis.Case presentationWe report the case of a child that presented chronic constipation, encopresis and mycrocephaly. The characteristics were initially compatible with a case of functional constipation and a therapy with polyethylene glycol was prescribed. After a year, because of poor response, a plain abdominal X-ray was performed, detecting sacrum abnormalities. Finally, a CGH-array analysis was performed and a form of Currarino Syndrome caused by a rare 7q36 microdeletion, was diagnosed.ConclusionOccult spinal dysraphism should be suspected in case of poor polyethylene glycol responder constipation, even when evident sacral abnormalities on the physical examination are not detected.