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C Camaschella

Publications and source records attributed to C Camaschella.

136 records · Page 8Linked to original sources
PubMedDate not supplied

Screening of beta-thalassemia mutations by PCR and ASO analysis in an Italian population of mixed geographic origin.

We used the polymerase chain reaction (PCR) and allele-specific-oligonucleotide hybridization (ASO) or restriction enzyme analysis (RE) to investigate the molecular defect in 100 Italian subjects heterozygous for beta-thalassemia, members of 50 couples at risk for the disease: 93 out of the 100 alleles studied were identified after investigating 9 known mutations. The mutation was identified in both members of the couple in 43/50 cases; in the remaining 7 couples the defect was identified only in one subject. The PCR-ASO or-RE method is a suitable, though still complex, approach to prenatal diagnosis of beta-thalassemia in a population with heterogeneous molecular defects.

Alleles↗
PubMedDate not supplied

Thalassemia intermedia.

Thalassemia intermedia is a clinical definition applied to patients whose clinical phenotype is milder than that of thalassemia major. Criteria used to define thalassemia intermedia including age at presentation, hemoglobin or fetal hemoglobin levels and transfusion independence, are unsatisfactory. The possibility of typing the molecular defect allows a retrospective analysis of patients and offers a new tool for the diagnosis of thalassemia intermedia. Nevertheless, because of several factors that interact in the disease expression, the beta-genotype alone is not predictive of the phenotype in all cases. Although benign, the clinical course of thalassemia intermedia is characterized by several complications that can be prevented by an accurate follow-up. The conventional treatment of thalassemia intermedia remains controversial; it is hoped that recent advances in the pharmacological manipulation of hemoglobin switching will offer a therapeutic option in the future, at least to selected patients.

Heterozygote↗
PubMedDate not supplied

Serum erythropoietin and circulating transferrin receptor in thalassemia intermedia patients with heterogeneous genotypes.

BACKGROUND: Thalassemia intermedia patients usually do not require blood transfusions; however, all show variable degrees of erythropoietic marrow expansion to compensate for more or less marked anemia, and this represents the major cause of complications in untransfused individuals. MATERIALS AND METHODS: To assess the degree of erythropoietic expansion in thalassemia intermedia, serum erythropoietin (sEpo) and serum transferrin receptor (sTfr) were determined in thirty Italian patient's characterized by their beta-globin genotype. RESULTS: Six patients showed inappropriately low sEpo levels (O/P ratio < 0.85). Even excluding these cases, no clear relationship was observed between Hb levels and sEpo or sTfr. Two groups of patients were compared: the first with low HbF (< 40%) that included the majority of beta(+) genotypes, and the second with high HbF (> 40%) that contained a prevalence of beta(0) genotypes. Hb levels were similar in the two groups: 8.09 +/- 1.15 g/dL in low HbF and 8.82 +/- 1.28 g/dL in high HbF patients. Mean sEpo was 112 +/- 78.02 mU/mL (O/P ratio = 0.98 +/- 0.22) in the first and 246.62 +/- 184.30 mU/mL (O/P ratio = 1.25 +/- 0.30) in the second group, with a statistically significant difference, as expected, because of HbF oxygen hyperaffinity. No significant difference in sTfr levels was observed, indicating a comparable erythropoietic response in the two groups. CONCLUSIONS: The relationships between anemia, HbF and total erythropoiesis in thalassemia are more complex than expected. Further studies of subjects with high HbF and benign conditions, such as HPFH, could be of help in clarifying this point, to the aim of safely increasing HbF in thalassemia intermedia.

Adult↗
PubMedDate not supplied

Hereditary hemochromatosis: recent advances in molecular genetics and clinical management.

BACKGROUND AND OBJECTIVE: Hereditary hemochromatosis (HC) is an inborn error of iron metabolism leading to increased intestinal iron absorption and progressive iron overload. There have been definite advances in our knowledge of the pathogenesis and management of idiopathic hemochromatosis in recent years, which prompted us to review this subject. INFORMATION SOURCES: The material examined in the present review includes articles and abstracts published in the journals covered by the Science Citation Index and Medline. In addition, both authors have been working in this field for several years and have contributed twelve of the papers cited in the references. STATE OF ART AND PERSPECTIVES: The disease is a late onset autosomic recessive condition, especially frequent in Caucasians. If unrecognized, severe clinical symptoms develop in mid-life related to organ failure. Early diagnosis prevents complications, since an intensive phlebotomy course removes excess iron and offers patients a normal life expectancy. Transferrin saturation is the first examination step, but liver biopsy is still essential for diagnosis and prognosis of HC. The biochemical defect is unknown. Positional cloning of the HC gene has led to the isolation of all the candidate region on the short arm of chromosome 6, telomeric to HLA-A. Recently a putative HC gene has been cloned from this region and found to be mutated in a large proportion of patients. The gene, known as HLA-H, is an atypical MHC class I gene. Although its biological function remains unknown, HLA-H is the first strong HC candidate gene. Molecular screening of patients and carriers is now possible in a significant portion of cases, thereby permitting better control of the disease. If it is unequivocally confirmed that the HLA-H gene is responsible for the disease, understanding of its biological function will provide information on the type and activity of the involved protein, revealing new insights into iron uptake and metabolism in humans.

Adult↗
PubMedDate not supplied

Feasibility of molecular diagnosis of alpha-thalassemia in the evaluation of microcytosis.

Microcytosis is a common hematological finding, usually related to iron deficiency or beta-thalassemia. When both of these conditions are excluded, alpha-thalassemia must be considered in the differential diagnosis. No simple biochemical test is able to diagnose the alpha-thalassemia trait. Using PCR amplification of the breakpoint in deletional forms, and amplification of the alpha 2 gene and restriction enzyme digestion in non-deletional forms, we identified the alpha-thalassemia carrier status in 42 out of 51 (82%) patients with microcytosis or slight microcytic anemia, unrelated to iron deficiency or beta-thalassemia. Our results underline the usefulness of molecular tests in clinical practice.

Anemia, Iron-Deficiency↗
PubMedDate not supplied

Juvenile and adult hemochromatosis are distinct genetic disorders.

Juvenile Hemochromatosis (JH) is a rare genetic disorder that causes iron overload. JH clinical features are similar to those of hemochromatosis (HFE), but the clinical course is more severe and is characterized by an earlier onset and by a prevalence of cardiac symptoms and endocrine dysfunctions. Here we describe seven Italian patients belonging to five unrelated families with clinical features typical of JH. In four out of five families the parents were consanguineous. Analysis of HFE gene mutations in all the cases and nucleotide sequence of the gene in one case excluded this gene as responsible for JH. Segregation analysis of 6p markers closely associated with HFE in families with consanguineous parents clearly showed that JH is unlinked to 6p and thus genetically distinct from HFE.

Adolescent↗