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In this study, we determined the genotype frequencies of polymorphisms of cytokine genes and investigated their association with the risk of respiratory distress syndrome (RDS) in preterm infants. Genetic polymorphisms in the cytokines interleukin (IL)-10, IL-8, and tumor necrosis factor (TNF) alpha, were studied in 342 white Italian newborns (112 without RDS, 66 prematurely born with RDS, and 164 infants born at term who were included as healthy controls). The polymorphisms were analyzed by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). The IL-10 mRNA levels were analyzed according to genotype by quantitative real-time PCR (QRT-PCR) in Epstein-Barr virus-transformed lymphoblastoid cell lines (EBV-LCLs) of 42 full-term healthy infants. Logistic regression analysis demonstrated the risk of RDS to be significantly lower in preterm infants with an IL-10 -1082 GG/GA genotype than in those with an AA genotype [odds ratio (OR) = 0.48, 95% confidence interval (CI): 0.24-0.95, p = 0.03]. QRT-PCR analyses showed that the IL-10 mRNA levels were significantly higher in 27 IL-10 -1082 GG/GA carriers compared with 15 IL-10 -1082 AA carriers (p = 0.03). We conclude that the IL-10 -1082 GG/GA polymorphism may have a role in RDS development in premature infants.

The status of the CDKN2A gene family, including CDKN2A, CDKN2B, and CDKN2C, was investigated in 24 cases of neuroblastoma. These genes were selected on the basis of 1) high incidence of their inactivation in several human cancers and 2) their localization on chromosomal regions (9p and 1p) frequently rearranged in neuroblastomas. Detailed molecular analyses indicated the absence of homozygous deletions and point mutations involving these genes in all investigated tumor samples. However, when loss of heterozygostity for chromosome 9p21 (the region where CDKN2A and CDKN2B are localized) was investigated, 16% of cases showed abnormalities in an area telomeric to the CDKN2A locus. To study transcriptional silencing of the CDKN2A gene, the methylation status of exon 1 was examined. In about 35% of cases, a partial methylation was evidenced. Analysis of the CDKN2A mRNA expression, however, did not show any relationship between methylation status and gene transcription. Finally, expression of the CDKN2B gene was demonstrated in all stage IV neuroblastomas, whereas none of stage I tumors expressed this gene. This finding suggests the occurrence of a correlation between CDKN2B transcription and tumor phenotype.

Congenital dyserythropoietic anemia type II (CDA-II) is the most frequent form of CDA. The inheritance pattern is autosomal recessive and its prevalence as well as the frequency of the gene are still unknown; this is due to the heterogeneity of clinical manifestations and to the fact that the majority of cases were probably undiagnosed.

Hereditary Spherocytosis (HS) is a common hemolytic anemia characterized by a chronic hemolysis with a broad spectrum of clinical severity. The red cells present a varying degree of surface area deficiency resulting in a spherocytic phenotype and increased osmotic fragility. It is now recognized that this disorders is associated with defects of the erythrocyte membrane skeleton. Spectrin, the most abundant skeletal protein, consistes in two chains, α and β, intertwined in an antiparallele manner to form heterodimers which associate at their head region to form tetramers. This skeletal network plays an essential role in determining the shape and deformability of the red cell.

α-spectrin synthesis exceeds s by a factor four (Hanspal, 1987). This suiemeni suggests that α-spectrin deficiency would be evident only in the homozygous slate. Agre (1982, 85) described some cases of recessivcly inherited HS characterized by severe spectrin deficiency and life-threatening hemolysis. Marchcsi (1989) founded in 9 out of 20 of these kindreds an acidic shift of αII domain. More recently Forget (1990) analyzing the genomic DNA of these subjects demonstrated an Ala-Asp (GAT-GCT) substitution at position 972 of α-sp. In order to assess clinical findings of rHS and verily the linkage with α-spccirin gene we studied 11 unrelated kindreds of Italian extraction, characterized by affected propositus with hematologic ally and biochemically normal parents. Two of these had severe HS, whereas the remaining have a clinical picture of typical HS, We examined 3 polymorphic sites (Xbal, PvuII, MspI) founded in linkage disequilibrium with α-sp gene (Hoffman, 1987)(3021-EI cDNA probe was given by courtesy of B.C.Forget). In the informative families rHS is associated with the following liaplotypc X(+), P(-), M(+) in three chromosomes and with ++-, -+- and – in three others. The haplotypc ++ is the most frequent in normal population of our country. This finding suggests the heterogeneity of molecular defect at the α-gene level. Furthermore in two cases the haplotype assignement allows lo the exclusion of α-sp gene involvement. This suggests thai lite α-spectrin gene abnormalities couldn't cause all rHS.