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C Camaschella

Publications and source records attributed to C Camaschella.

At least 91 records · Page 5Linked to original sources
PubMed1990

Haplotype distribution and molecular defects at the phenylalanine hydroxylase locus in Italy.

In order to investigate the molecular basis of phenylketonuria (PKU) in Italy, we characterized the RFLP haplotypes at the phenylalanine hydroxylase gene in 38 unrelated Italian PKU families. The distribution of haplotypes associated with PKU alleles differs from that of other European populations. In particular, haplotypes 1 and 6 are present in 39.7% and 17.6% of the PKU chromosomes, whereas the frequencies of haplotypes 2 and 3 are 5.9% and 2.9%, respectively. The characterization of PKU mutations using the polymerase chain reaction and allele-specific oligonucleotides shows that 1 out of 2 haplotypes 3 carries the splicing mutation and that 2 out of 4 haplotypes 2 carry the missense mutation associated with these haplotypes in North European populations. Our results indicate that the two molecular defects most frequent in Northern Europe represent a minority of PKU mutations in Italy.

Gene Frequency↗
PubMed1989

The homozygous state of G to A--117A gamma hereditary persistence of fetal hemoglobin.

During a study of Sardinian families with hereditary persistence of fetal hemoglobin (HPFH), two unrelated subjects with unusually elevated Hb F levels were identified. By selective amplification of the A gamma gene promoter and hybridization to synthetic oligonucleotides, we demonstrate that these subjects are homozygous for the -117A gamma G----A substitution that is responsible for a form of nondeletional HPFH. The hemoglobin synthetic pattern of these patients is discussed.

Adult↗
PubMed1989

RFLPs of the phenylalanine hydroxylase gene in the Italian population.

Different mutations of the phenylalanine hydroxylase (PAH) gene leading to phenylketonuria (PKU) have been described associated with specific haplotypes in several European countries. In order to investigate the distribution of DNA haplotypes in Italy, restriction fragment length polymorphism (RFLP) analysis of the PAH gene was performed in nine Italian PKU patients from eight unrelated families, and in the available relatives. The analysis of eight polymorphic sites revealed haplotypes 1 and 6 in association with PKU. This pattern appears to differ from those reported for other European populations. The majority of the 14 PKU subjects studied showed compound heterozygosity for different haplotypes, as observed for other European series. RFLP analysis at the PAH locus allowed us to offer the possibility of prenatal diagnosis to six of the studied families. One prenatal diagnosis was performed and a normal fetus was diagnosed.

Alleles↗
PubMed1989

Molecular characterization of Italian chromosomes carrying the Lepore Boston gene.

Hemoglobin Lepore Boston is characterized by abnormal non-alpha-chains that are the product of a fusion delta beta gene originated from an unequal crossing over between misaligned delta and beta genes. The investigation of the restriction fragment length polymorphisms (RFLP) of the beta-globin gene cluster in 18 Italian Lepore Boston chromosomes indicates that the hybrid gene is linked to two RFLP patterns. The majority of chromosomes show a pattern which corresponds to haplotype V and a minority to haplotype I according to Orkin's classification. A single Hb Lepore Boston homozygote was homozygous for haplotype V. The two haplotypes differ only for a single site 3' to the beta cluster. Our data allow the speculation that in Italy the Lepore Boston gene might be the result of multiple recombination events.

Chromosome Deletion↗
PubMed1989

Hypothalamic pituitary adrenal function in patients with thalassemia major.

We examined the adrenocortical function in 14 italian thalassemic patients (8 f., 6 m.) aged 12 to 28. The following hormones were determined in each subject: plasma cortisol and aldosterone levels in both basal conditions and after maximal and submaximal stimulus (250 and 5 micrograms respectively) with synthetic corticotrophin beta 1-24 (Synacthen Ciba); corticotrophin and cortisol response to insulin-induced hypoglycaemia (0.15 U/kg iv.). Tests were repeated in all patients four years later. Normal controls were a group of 10 normal subjects matched for age, sex and body mass. Normal basal values of cortisol, aldosterone and ACTH were observed. Impaired cortisol response after stimulation with 5 micrograms of ACTH (6 patients) and after hypoglycaemia (4 patients) was identified. At the second test, four years later, one patient showed impaired cortisol response to both ACTH (5, micrograms) and hypoglycaemia, unlike the normal response to the first test. In all the others the cortisol response to stimulation did not differ from previous ones. In conclusion reduced ACTH and cortisol reserves detected in some thalassemic patients may be related to iron infiltration in the pituitary and adrenal glands. However, the present study did not indicate any significant correlation between either total blood load or serum ferritin and adrenal function parameters. Alteration in circulating hormones catabolism and impaired synthesis of transport proteins caused by chronic liver disease made adrenocortical hypofunction an even more complex picture to understand.

Adolescent↗
PubMed1988

Circulating 'trophoblast' cells in pregnancy have maternal genetic markers.

A syncytiotrophoblast-associated antigen identified by the monoclonal antibody (McAb) H315 is detectable on the surface of a low proportion of peripheral blood cells in pregnant women, raising the possibility of a new approach to prenatal diagnosis of genetic disorders. We aimed at verifying the trophoblastic origin of H315+ cells and their use for prenatal diagnosis of beta-thalassaemia. H315+ cells were separated from the peripheral blood of pregnant women: the DNA obtained from these cells in two selected cases was shown to have genetic markers indistinguishable from those of the mother and definitely different from the fetus. Our results suggest that H315 antigen is expressed by maternal cells and that prenatal diagnosis on peripheral blood of the mother using H315 McAb is not feasible.

Antibodies, Monoclonal↗
PubMed1988

A frequent A gamma-hereditary persistence of fetal hemoglobin in northern Sardinia: its molecular basis and hematologic phenotype in heterozygotes and compound heterozygotes with beta-thalassemia.

A survey of hemoglobinopathies in northern Sardinia revealed a high frequency (0.3%) of carriers of a hematologic condition characterized by increased expression of fetal hemoglobin during adult life (hereditary persistence of fetal hemoglobin or HPFH). In spite of a normal hematologic phenotype, the heterozygous carriers for this condition display about 12% HbF, almost exclusively of the A gamma type; compound heterozygotes with beta-thalassemia have 20%-26% HbF and run a very mild clinical course. The sequence analysis of the cloned A gamma gene linked to the HPFH determinant revealed the presence of a G----A substitution at position -117 of the A gamma-globin gene promoter; the same mutation occurs also in Greek HPFH, although associated with different restriction polymorphisms. Another hereditary condition characterized by increased HbF (alpha 2 A gamma 2) level and a mild thalassemia phenotype in Sardinia is associated with the -196C----T substitution in the A gamma-globin gene promoter (Sardinian delta beta-thalassemia). Population studies using oligonucleotides complementary both to the -117 G----A and -196C----T mutations and the corresponding normal sequences confirm the presence of these mutations only in HPFH and delta beta-thalassemia chromosomes and exclude these changes being common DNA polymorphisms.

Female↗
PubMed1988

Distribution of Ha-RAS-1 proto-oncogene alleles in breast cancer patients and in a control population.

The frequencies of 13 different Ha-ras proto-oncogene alleles have been estimated in 92 breast cancer patients and 60 unaffected individuals. The Ha-ras alleles can be identified using a DNA restriction fragment length polymorphism (RFLP) closely linked to the 3' end of the gene, and are characterized by a different length due to a region of sequences repeated a variable number of times (variable tandem repeats, VTR). The statistical analysis of the data obtained shows that the frequency of alleles ranging between specific length limits is significantly higher in breast cancer patients than in controls. The same applies to specific genotypes bearing the aforementioned alleles. This suggests that the inheritance of these alleles may be associated with an increased risk of developing breast cancer.

Adult↗
PubMed1988

Meiotic recombination in the beta globin gene cluster causing an error in prenatal diagnosis of beta thalassaemia.

In the course of a prenatal diagnosis for beta thalassaemia by linkage analysis of restriction fragment length polymorphisms, a homozygous beta thalassaemia fetus was misdiagnosed as beta thalassaemia trait. Extensive studies of the polymorphic sites within the beta globin gene cluster in all the members of the family resulted in the conclusion that the paternal chromosome 11 of the newborn was different from that expected. Paternity was confirmed by HLA typing and blood group studies. The analysis of another polymorphic locus on chromosome 11 within the family was in agreement with the possibility of a crossing over between the two paternal chromosomes in a region 5' to the beta gene, previously indicated to contain a 'hot spot' area for recombination. This report underlines the risk of performing prenatal diagnosis using restriction polymorphisms 5' to the beta gene.

Diagnostic Errors↗
PubMed1988

Delineation of specific beta-thalassemia mutations in high-risk areas of Italy: a prerequisite for prenatal diagnosis.

In this study, we defined by haplotype characterization combined with oligonucleotide hybridization or direct restriction endonuclease analysis the specific beta-thalassemia mutations in a representative sample of beta-thalassemia chromosomes from patients with homozygous beta-thalassemia originating from different parts of Italy. We characterized the mutations in 90% of the thalassemia chromosomes and found that three mutations, namely the beta(+)IVS 1-110, beta (0)-39 and beta(+)IVS 1-6 are prevalent in the Italian population. Most of the patients investigated were compound heterozygotes for two beta-thalassemia mutations, and only a few were homozygotes for one mutant. On the basis of these findings, we predict that prenatal diagnosis in this population would be feasible in most cases by fetal DNA analysis with the oligonucleotide method using a limited number of oligonucleotide probes selected after screening parents for the most common beta-thalassemia mutations. We have also devised a method based on hybridization with a mixture of two oligonucleotides that allows rapid and simultaneous screening of prospective parents for the two most frequent mutations in Italians, the beta(+)IVS 1-110 and beta(0)-39 mutants. This method may be applicable to prenatal diagnosis in cases at risk for the genetic compound of these mutations.

DNA Mutational Analysis↗
PubMed1987

A benign form of thalassaemia intermedia may be determined by the interaction of triplicated alpha locus and heterozygous beta-thalassaemia.

In this paper we report that the combination of a triplicated alpha globin locus with heterozygous beta-thalassaemia produces a clinical phenotype of thalassaemia intermedia in five Italian subjects from four unrelated families, while in two other cases the phenotype was thalassaemia minor. The haematological findings of the five patients were uniform, producing a benign form of thalassaemia intermedia, transfusion independent, with a long life expectancy. The pattern of inheritance of the two genetic determinants and the more pronounced beta/alpha globin chain imbalance, demonstrates that the genetic combination is indeed the cause of the phenotype. The pattern of restriction enzyme site polymorphisms suggests the presence of the beta IVS I 110 G----A mutation at least in three of these cases.

Adolescent↗
PubMed1987

The 3' ends of the deletions of Spanish delta beta zero-thalassemia and black HPFH 1 and 2 lie within 17 kilobases.

Spanish delta beta zero-thalassemia, a mild thalassemic condition characterized by increased level of hemoglobin (Hb) F production during adult life, is known to be due to a large deletion starting within the beta globin gene cluster and extending beyond the 3' breakpoint of any other similar deletional defects so far identified. By molecular cloning and by genomic mapping we now demonstrate that the deletion of Spanish delta beta zero-thalassemia ends at approximately 11 and 17 kilobases (kb) downstream to the 3' endpoints of black hereditary persistence of fetal hemoglobin (HPFH) type 1 and 2, respectively. As suggested by the complete characterization of this and other deletional defects involving the beta globin gene cluster, the 5' and 3' breakpoints of several deletions cluster in rather restricted DNA areas, further strengthening the idea that common molecular mechanisms may operate in causing these deletions.

Base Sequence↗