ABSTRACT
Congenital dyserythropoietic anemia type I (CDAI) is an autosomal recessive inherited haematological disorder associated with moderate-to-severe anemia characterized by ineffective erythropoiesis with distinct morphological abnormalities in erythroid precursors. We present two case of congenital dyserythropoietic anemia type I in two Sicilian patients heterozygous for ß0 39 globin gene cod 39 C > T with marked bone marrow abnormalities, responding to treatment with alpha interferon. The diagnosis was established using routine haematological and biochemical test, light and electron microscopy; molecular analysis of the CDAN1 gene associated to the CDAI disease was performed. The response to the treatment was monitored using the hemoglobin levels, the red cell count, the reticulocyte count and the transfusional requirement. This report points out the usefulness of the treatment with interferon alpha in two Sicilian beta thalassemia carriers, in which the therapy was well tolerated without producing any side effects; in these patients the transfusion requirements after the initiation of interferon therapy decreased.
ABSTRACT
The increasing number of cystic fibrosis (CF) mutations is a great obstacle to the use of DNA procedures in the detection of gene defects. We describe a fast, cheap and non-radioactive procedure, Reverse dot-blot analysis (RDB), for the simultaneous detection of CF mutations in the Italian population. We used this approach to study seven exons of the CF gene for 14 CF gene defects and were able to characterize 222 of 272 CF chromosomes (80%). The cost of the procedure was $25 per sample analysed.
Subject(s)
Cystic Fibrosis/genetics , Mutation , Point Mutation , Polymerase Chain Reaction , Alleles , Base Sequence , DNA Primers , Exons , Humans , Italy , Molecular Sequence Data , Nucleic Acid Hybridization , Sequence DeletionABSTRACT
Three intragenic microsatellites of the CFTR gene, a TA and a CA repeats, namely IVS17bTA and IVS17bCA, located in intron 17b and a CA repeat (IVS8CA) located in intron 8 of the CFTR gene, were analyzed in a large sample of Italian cystic fibrosis (CF) and normal chromosomes. Linkage disequilibrium was evaluated between each marker and difference CF mutations on a total of 377 CF and 358 normal chromosomes. Our results are consistent with the hypothesis that all delta F508 chromosomes derive from a single mutational event. The same hypothesis is valid for mutations G542X, N1303K, 1717-1G-->A, which might have been originated more recently than delta F508.
Subject(s)
Cystic Fibrosis/genetics , DNA, Satellite/genetics , Linkage Disequilibrium , Mutation , Cystic Fibrosis Transmembrane Conductance Regulator , Genetics, Population , Haplotypes , Humans , Italy , Membrane Proteins/genetics , Models, Genetic , Oligodeoxyribonucleotides/genetics , Repetitive Sequences, Nucleic AcidABSTRACT
Prenatal diagnosis of haemoglobin disorders is accepted to be a useful procedure to avoid births of infants with homozygous diseases. Advances in sampling and molecular techniques, such as polymerase chain reaction (PCR) and chorionic villus sampling (CVS), have made earlier and safer first-trimester prenatal diagnosis possible. However, these procedures need previous studies of at-risk couples, which can be very time-consuming when a number of different beta-thalassaemia mutations occur in the region. We describe the possibility of making a first-trimester prenatal diagnosis by cordocentesis and fetal blood analysis at the 12th week of gestation. We found no statistically significant difference (p greater than 0.05) between beta/gamma values in fetuses at the 12th and 18th weeks of gestation. In seven affected fetuses aborted at the 12th week of gestation, the diagnosis was confirmed in all cases by PCR analysis. These findings suggest that early cordocentesis could be an alternative procedure to CVS and PCR analysis.
Subject(s)
Fetal Blood/chemistry , Prenatal Diagnosis/methods , Thalassemia/diagnosis , Female , Follow-Up Studies , Genotype , Hemoglobin A/analysis , Humans , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Pregnancy , Pregnancy Trimester, First , Reproducibility of Results , Thalassemia/geneticsSubject(s)
Mutation , Thalassemia/genetics , Codon , Genotype , Haplotypes , Humans , Prenatal Diagnosis , Sicily , Thalassemia/diagnosisABSTRACT
The authors report 8 diagnostic cordocentesis performed at the end of the first trimester. The indication was thalassemia (5 cases) and karyotyping (3 cases). The technique requires that the operator holds both the probe and the needle (25 G X 90 mm); the fetal blood sample ranged between 0.25 and 0.35 cc, sufficient in all cases for the diagnosis. 1 pregnancy was terminated on the basis of the diagnostic result; no complications reported at a 3-weeks follow-up in the remaining 7 patients. The first trimester cordocentesis offers several advantages if compared to CVS, especially for thalassemia prenatal diagnosis; furthermore it opens new perspectives for intrauterine transplantations. More experience is required to assess the safety of the procedure.
