In this study, we report the results of haplotype and mutation analysis of the ATP7B gene in Wilson disease (WD) patients of Greek origin. We have analysed 25 WD families and two single patients and characterised 94% of the WD chromosomes investigated. We have found 12 different molecular defects (three frameshifts, two splice site, two nonsense, five missense mutations), four of which are novel. Five of the mutations are widely prevalent accounting for 74% of the WD chromosomes analysed. These results may enable preclinical diagnosis in the large majority of WD patients of Greek descent, thereby improving genetic counselling and disease management.

Adolescent↗

PubMedDate not supplied

Mucoepidermoid carcinoma of the bronchus.

Bronchoscopy in a 4.5-year-old girl with recurrent pneumonia showed an exophytic endobronchial mass. Biopsy disclosed microscopic and ultrastructural features of a low-grade mucoepidermoid carcinoma. Complete cure was accomplished by surgical removal of the tumor and right lower lobe.

Adolescent↗

PubMedDate not supplied

Quantification of liver iron overload by T2 quantitative magnetic resonance imaging in thalassemia: impact of chronic hepatitis C on measurements.

PURPOSE: Measurement of liver T2 values seems to be an accurate and sensitive magnetic resonance imaging (MRI) method for the quantification of liver hemosiderosis in multiple transfused patients with thalassemia. Because many of these patients have coexistent chronic hepatitis C virus (HCV) infection, the effect of inflammatory changes on liver T2 values was assessed. MATERIALS AND METHODS: Liver MRI studies of 35 HCV+ and 17 HCV- patients with beta-thalassemia, 9 HCV+ patients without thalassemia, and 10 healthy controls of the same age range (13 to 32 years) were reviewed. Iron status was assessed by serum ferritin in all patients, and determination of liver iron concentration (LIC) was available in 16 HCV+ patients with thalassemia. Histologic activity index (HAI) and grades of siderosis were evaluated in all HCV+ patients with thalassemia. RESULTS: Patients with thalassemia had significantly lower T2 values (P < 0.0001) than subjects without thalassemia, whereas no difference existed between HCV+ patients without thalassemia and healthy controls. In HCV+ patients, LIC correlated more nearly with T2 values (r = 0.93) than with serum ferritin (r = 0.73). T2 values were not influenced by HAI score or fibrosis. CONCLUSION: Liver T2 values were found to be more accurate than serum ferritin in predicting liver iron overload and were not influenced by the presence of chronic hepatitis C. Therefore, MRI could serve as a noninvasive alternative to liver biopsy for the quantification of hemosiderosis in HCV+ patients with thalassemia.

Adolescent↗

PubMedDate not supplied

Hematologic phenotype of the mutations IVS1-n6 (T-->C), IVS1-n110 (G-->A), and CD39 (C-->T) in carriers of beta-thalassemia in Greece.

The hematologic phenotype was characterized in heterozygotes for three of the most common beta-thalassemia mutations in the Greek population. The study included 17 carriers of beta++ IVS1-n6 (T-->C), 21 carriers of beta+ IVS1-n110 (G-->A), and 17 carriers of beta 0 CD39 (C-->T). The 55 beta-thalassemia heterozygotes were selected from among parents of patients on regular transfusion regimens, and the beta-thalassemia mutation was identified by means of the polymerase chain reaction to amplify the appropriate region of the beta-globin gene and then by allele-specific oligonucleotide hybridization. The assessment of hematologic phenotype included complete blood count and quantitation of hemoglobin HbA2 and HbF and of the globin chain biosynthesis ratio. Comparison and statistical analysis of the hematologic parameters for the three mutations demonstrated no consistent correlation among the three mutations relative to Hb levels, hematocrit, and red cell indices, although heterozygotes for the IVS1-n6 mutation produce red blood cells with slightly higher mean corpuscular volume; significantly lower values of HbA2 (mean, 3.81% +/- 0.62% with four values less than 3.60%) in IVS1-n6 heterozygotes compared with IVS1-n110 heterozygotes (mean, 4.69% +/- 0.48%) and CD39 heterozygotes (mean, 4.75% +/- 0.50%, P < 0.001); and significantly higher HbF levels in CD39 heterozygotes (mean, 2.31% +/- 1.52%) compared with IVS1-n6 heterozygotes (mean, 0.79% +/- 0.45%, P < 0.01) and IVS1-n110 heterozygotes (mean, 1.17% +/- 0.75%, P < 0.01). With respect to the HbA2 levels, the findings are in agreement with previous studies in Mediterranean populations; the slightly higher levels of HbF in CD39 heterozygotes appear to be reported for the first time.

Alleles↗

PubMedDate not supplied

Molecular characterization of homozygous (high HbA2) beta-thalassemia intermedia in Greece.

Homozygous beta-thalassemia is usually characterized by severe anemia requiring regular blood transfusion for survival. For homozygous patients with milder clinical manifestations and no dependence on transfusion therapy, the term thalassemia intermedia is usually applied. Genetic mechanisms that may ameliorate the clinical expression of homozygous beta-thalassemia include coinheritance of alpha-thalassemia, inheritance of mild beta-globin gene mutations, and increased gamma-globin chain production, which may partially compensate for the lack of beta-globin chain synthesis. To identify which of these factors may contribute to the modification of childhood homozygous, high-hemoglobin A2 (HbA2) beta-thalassemia in Greece, the interaction of alpha-thalassemia, types of beta-thalassemia mutations, and the presence of a polymorphic site 5' to the G gamma-globin gene, which has been described as associated with increased gamma-globin chain production in some cases, was assessed. The results were analyzed in light of similar studies in 150 randomly selected, homozygous, high-HbA2 beta-thalassemia patients with the aim of assessing whether thalassemia genotypes can provide information useful for prognosis and/or more appropriate management of homozygous beta-thalassemia patients. The results indicate that, in general, the major factor modifying the clinical expression of homozygous, high-HbA2 beta-thalassemia in Greece is the inheritance of mild beta-thalassemia mutations. Although there is not always a complete correlation of genotype with clinical phenotype, the inheritance of two mild beta-thalassemia alleles results in almost all cases (11 of 12 cases in this study) in thalassemia intermedia phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

PubMedDate not supplied

Tissue oxygenation in patients with hemoglobinopathy H.

To evaluate the degree of tissue hypoxia in patients with hemoglobinopathy H disease, whole blood oxygen affinity was estimated and analyzed in 33 patients. Twenty patients with iron deficiency anemia, matched for degree of anemia, served as controls. The results were as follows: Whole blood oxygen equilibrium curves of patients with HbH disease are biphasic because of a combination of the rectangular hyperbolic curve of HbH and the normal sigmoid curve of HbA and are shifted toward the left (P50 3.66 +/- 0.33 kPa). Patients with iron deficiency anemia have right-shifted oxygen equilibrium curves (P50 4.02 +/- 0.13 kPa) compared with normal. Oxygen release to the tissues in HbH disease is decreased (1.4 +/- 0.3 mmol/L) as compared with iron-deficient patients (1.6 +/- 0.2 mmol/L) with a similar degree of anemia. Red cell indices vary between the two groups. In patients with HbH disease the mean corpuscular hemoglobin concentration was 268 +/- 17 g/L as compared with 294 +/- 18 g/L in iron deficiency anemia. These findings indicate that whole blood oxygen affinity is a reliable index of tissue oxygenation in patients with hemoglobinopathy H.

Anemia, Iron-Deficiency↗

PubMedDate not supplied

Tissue immunodetection of c100 hepatitis C virus antigen in major thalassemic patients.

BACKGROUND/AIMS: Hepatitis C Virus (HCV) detection in the livers of chronically infected patients remains a debatable issue. To determine the significance of hepatic expression of hepatitis C viral antigen c100, an immunohistochemical assay was performed in 113 young thalassemics with chronic HCV infection. METHODOLOGY: One hundred and thirteen patients were seropositive for antibody to HCV by second-generation testing. The monoclonal antibody TORDJI-22 was used in an alkaline phosphatase 3-step staining method, and any possible association between the results of HCV immunodetection and various clinicopathologic variables was investigated by univariate and multivariate statistical analysis. In 36 cases, post-therapy liver biopsy specimens were also studied. RESULTS: HCV c100 antigen was detected in 62% of all pretherapy samples, exclusively in the cytoplasm of rather few hepatocytes. Its expression was positively associated with male gender (p = 0.02) as well as with rather advanced age (p = 0.03) and was frequently accompanied by low necroinflammatory scores (according to the modified HAI grading). At the end of interferon-alpha (IFN-alpha) therapy, the immunoreactive prevalence of c100 antigen decreased significantly (pF = 0.002). CONCLUSIONS: We conclude that hepatic expression of c100 antigen is detected in a considerable percentage of thalassemics but it is not likely to provide information concerning the viral load in the infected liver. IFN therapy appears to reduce the hepatic expression of this viral antigen in thalassemic patients.

Adolescent↗

PubMedDate not supplied

RNase H of human leukemic cells: a new biological parameter in the study of human leukemias (review).

This article reviews the authors' investigation of the enzyme RNase H (EC 3.1.4.34.) in human leukemic cells and presents the accumulated available data, based on which this enzyme is proposed to serve as a new biological parameter in the study of progression of human leukemias. The introduction gives a brief account of the occurrence, characterization and possible biological role of RNase H in cells and in retroviruses. The results reviewed briefly concern: (1) the development of a new convenient, economic and reliable assay for normal and leukemic blood mononuclear cell RNase H, which is capable of resolving subtle activity differences between samples; (2) the differentiation of RNase H levels between normal and leukemic cells; (3) the correlation of RNase H levels from different leukemia types with the severity of the disease; (4) the correlation of RNase H levels in leukemic cells with clonogenic stages in the clonal differentiation pathway; (5) the predictive potential of a RNase H activity-based parameter (phi) in assessing progression in acute myelocytic leukemia and (6) the possibility of differentiation of the RNase H levels between normal and leukemic cells via regulation of the enzyme activity at the level of antagonistic phosphorylations mediated by cAMP and calmodulin.

Endoribonucleases↗