PubMed Health⌕ Search

Biomedical subjects

A Angius

Publications and source records attributed to A Angius.

51 records · Page 3Linked to original sources
PubMed1981

Prevention of homozygous beta-thalassemia by carrier screening and prenatal diagnosis in Sardinia.

We report here results of a 3-year pilot voluntary screening program coupled with prenatal diagnosis directed to the prospective prevention of homozygous beta-thalassemia (beta-thal) in Sardinia. The screening program took two approaches: outreach community testing and hospital testing on request after a period of sensibilization. The outreach testing was very effective as, taking into account the already known number of couples at risk with an affected proband (20), 74% of the couple at risk expected (61) on the basis of the carrier rate were identified. Less effective was the hospital testing in which half of the couples at risk expected were detected (502 with the 199 without an affected proband). After nondirective genetic counseling, approximately 85% of the couples at risk, which had a pregnancy, with no statistically significant difference between those with and those without a proband, requested prenatal testing. This figure showed a steadily increase from the beginning in 1977 to 1980. All the pregnancies (42), but two carrying homozygous fetuses, were terminated on parental request. A continuous hospital survey of thal-major admissions in the different hospitals of the counties showed a steady decline in the incidence figure at birth from 1976 (1:213) to 1978 (1:290). These results showed that even in a medium-developed, rural, Catholic population screening coupled with prenatal diagnosis can be successful in the control of a fatal, recessively inherited disorder.

Adult↗
PubMed1981

Globin chain synthesis analysis in obligate beta 0-thalassemia heterozygotes with isolated increase of hemoglobin A2 levels.

Globin chain synthesis analysis was carried out in 14 obligate beta 0-thalassemia heterozygotes, i.e., parents of children with thalassemia major or intermedia due to homozygous beta 0-thalassemia, with almost normal red blood cell indices and isolated increase of Hb A2 levels. alpha/beta globin chain synthesis ratios were almost balanced or slightly reduced (0.62-1.30). This finding suggests that these heterozygotes carry both alpha- and beta-thalassemia genes. However, alpha-globin structural gene mapping by restriction enzyme analysis must be carried out to confirm this explanation.

Female↗
PubMed1980

Polymorphism of DNA sequence in the beta-globin gene region. Application to prenatal diagnosis of beta 0 thalassemia in Sardinia.

We used a restriction endonuclease to analyze the beta-thalassemia gene in Sardinia. When we digested human DNA with the restriction enzyme Bam HI, the beta-globin gene split into a 5' portion contained in a fragment of DNA 1.8 kb in length and a 3' portion in a fragment 9.3 kb in length. In some subjects, a variation in the nucleotide sequence affecting the site recognized by this enzyme on the 3' side of the beta-globin gene resulted in a different fragment, 22 kb in length, which contained the 3' portion of the beta-globin gene. In Sardinians without beta-thalassemia, the frequency of the 9.3-kb fragment was 0.67, and that of the 22-kb fragment was 0.33. In contrast, all the beta 0-thalassemia genes were associated exclusively with the 9.3-kb fragment. Thus, the beta 0-thalassemia lesion in Sardinians apparently arose on a chromosome that had the 9.3-kb Bam HI fragment. This observation can be used in prenatal diagnosis of beta 0-thalassemia in Sardina, since demonstration of the 22.0-kb fragment would indicate the normal beta-globin genotype and exclude the beta 0-thalassemia lesion on that chromosome. (N Engl J Med 302:185-188, 1980).

Base Sequence↗
PubMed1980

Prenatal diagnosis of beta thalassaemia by fetal red cell enrichment with NH4-Cl-NH4HCO3 differential lysis of maternal cells.

Prenatal diagnosis with globin chain synthesis analysis on fetal red blood cells concentrated by NH4Cl-NH4HCO3 differential lysis of maternal cells (Orskov lysis) was carried out in 27 pregnancies at risk for beta thalassaemia and one at risk for sickle cell beta0 thalassaemia. The beta/gamma globin chain synthesis ratio was also determined after anti-i-differential agglutination (12 cases), in almost pure fetal samples (sic cases) and by extrapolation (one case). Differential lysis permitted the study of samples drawn by placental aspiration containing as little as 3.2% fetal red blood cells. There was no consistent difference between the beta/gamma ratios observed after differentail lysis and those determined after the use of the other approaches. A presumptive diagnosis of homozygous beta thalassaemia was made in nine cases. All but one of these pregnancies was terminated. The absence of beta chain synthesis was confirmed by the study of fetal blood after abortion in four cases with suitable samples. Of the remaining pregnancies, six proceeded to term and non-homozygous infants were delivered. The others are still in progress. No fetal loss occurred. Orskov lysis seems to be a very reliable method for prenatal diagnosis of beta chain abnormalities. Moreover it can minimize the number and duration of placental aspirations required and thus the risk to the fetus.

Erythrocyte Count↗
PubMed1980

Prenatal diagnosis of beta thalassemia: experience with 133 cases and the effect of fetal blood sampling on child development.

Prenatal diagnosis was attempted in 133 pregnancies at risk for beta thalassemia (132 cases) or sickle-cell beta 0 thalassemia (1 case). Of these, 76 couples requested diagnosis because they already had children affected with homozygote beta thalassemia (72 cases) or beta+ thalassemia (4 cases). The others were probably at risk for beta 0 thalassemia since this is by far the predominant thalassemia type in Sardinia. Sufficient fetal blood for analysis was obtained by placental aspiration at 18--24 weeks gestation in 130 cases. Ten fetal losses occurred. The pregnancies were followed and no relevant complications were seen. Of the newborns delivered, 45 were followed from birth with particular attention to congenital malformation, neurological, growth, and maturity assessement. No major adverse effect of placentocentesis on child growth and development was observed. Placental samples were analyzed by globin chain synthesis analysis on carboxylmethylcellulose columns. When the placental samples contained more than 20% maternal red cells, fetal red cell enrichment was carried out by anti-i (53 cases) or anti-AB (2 cases) differential agglutination or NH4Cl-NH4HCO3 differential lysis of maternal cells (17 cases). Of the 130 cases, 32 fetuses had no beta-chain radioactivity and one had a beta/gamma ratio of 0.005. These were presumed to be homozygous and all but one were electively aborted. Absence of beta-chain radioactivity was confirmed in 10 abortuses with suitable cord blood samples. A total of 91 infants have been born and are nonhomozygous. Genotype assessment at 6 months after birth in 33 infants showed that there was only a slight overlap between the ranges of normal (0.095 +/- 0.016) and heterozygous (0.05 +/- 0.01) fetal beta/gamma globin chain synthesis ratios.

Blood Specimen Collection↗
PubMed1980

alpha-Thalassaemia in Sardinian infants.

A haemoglobin survey carried out in southern Sardinian newborn infants showed an overall incidence of 12.9% with haemoglobin Bart's of more than 1%. The distribution was trimodal: low (1 to 2%), intermediate (2 to 10%), and high (about 25%). A considerable overlap was seen between the first two groups. Both the 1 to 2% and 2 to 10% groups had thalassaemia-like red cell indices at birth. Newborn infants ascertained as having alpha-thalassaemia at follow-up did not necessarily have unbalanced alpha/non-alpha chain synthesis at birth. At follow-up examination two subjects in the 25% group had developed haemoglobin H disease, and the 2 to 10% group had thalassaemia-like red cell indices and unbalanced globin chain synthesis ratios indicative of heterozygous alpha-thalassaemia. The 1 to 2% group either had normal or slightly reduced alpha-chain synthesis ratios, indicative of the silent alpha-thalassaemia carrier state. Two subjects with 2.0% and 2.5% haemoglobin Bart's at birth had heterozygous beta-thalassaemia at follow-up. Therefore, they were double heterozygotes for alpha- and beta-thalassaemia with alpha/beta-globin chain synthesis ratios of 0.81 and 0.86. Genotype assessment in a few families showed that infants with haemoglobin Bart's levels of more than 2% may have one of the genotypes --alpha/ --alpha or -- --/alpha alpha.

Female↗
PubMed1980

Hematological characteristics of sardinian alpha-thalassemia carriers detected in a population study.

88 adults with thalassemia-like red cell indices, normal serum iron and normal hemoglobin (Hb) A2 and F levels, diagnosed in a mass screening had Hb H inclusion bodies studies (65 subjects) or Hb H inclusion bodies studies and globin chain synthesis analysis (23 subjects). The alpha/beta ratio of 0.70 +/- 0.10 was the same as in obligate alpha-thalassemia-1 (alpha-thal) carriers. Hb H inclusion bodies studies were found to be a reliable test for alpha-thal trait identification, resulting positive in approximately 70% of suspected carriers. The alpha-thal carrier defined by Hb H preparation or by globin chain synthesis had significant reduction in the mean Hb level, hematocrit, mean corpuscular hemoglobin and a significant increase in mean red cell count, but there was some overlap with controls.

Erythrocyte Count↗
PubMed1979

Interaction of alpha and beta thalassaemia genes in two Sardinian families.

Our paper describes two Sardinian families with alpha-beta thalassaemia interaction. In the first (family S), the propositus, whose haemoglobin pattern at birth consisted of about 25% Hb Bart's and 75% Hb F, successively developed a clinical and haematological picture typical of Cooleys anaemia. Haematological and globin chain synthesis studies together with these findings suggest that he is homozygous for beta 0 thalassaemia and heterozygous for alpha thalassaemia-1 and alpha thalassaemia-2. This conclusion is further substantiated by the finding of various combination of alpha and beta thalassaemia among his family members. In the P family two twins whose haemoglobin pattern and synthesis data at birth were similar to those of the proband of family S died in the neonatal period. The mother was assumed to be a compound heterozygte for alpha thalassaemia-2 and beta 0 thalassaemia and the father for alpha thalassaemia-1 and beta 0 thalassaemia. The homozygous state for beta 0 thalassaemia in association with the alpha thalassaemia 1 and alpha thalassaemia 2 genes results in a severe clinical picture similar to that of a homozygous beta 0 thalassaemia. The interaction between the heterozygous state for beta 0 thalassaemia and the alpha thalassaemia 1 or alpha thalassaemia 2 genes, or the combination of both, results in a haematological picture similar to that of a beta thalassaemia heterozygote.

Adolescent↗
PubMed1979

Prenatal diagnosis of beta-thalassaemia by fetal red cell concentration with anti-AB serum.

Prenatal diagnosis by globin chain synthesis analysis on fetal blood samples obtained by placental aspiration was performed in two pregnancies at risk for beta-thalassaemia. Since both fathers had blood group AB, and both mothers had group O, fetal red cell concentration from maternal-fetal mixtures was obtained with the aid of anti-AB serum. With this approach it was possible to carry out globin chain synthesis analysis with very small amounts of fetal blood. Heterozygous and normal genotypes were ascertained and confirmed after birth.

ABO Blood-Group System↗
PubMed1979

Beta 0 thalassemia trait in Sardinia.

The red cell indices and results of globin chain synthesis in peripheral blood of obligate beta 0 thalassemia (beta 0 thal) carriers (parents of homozygous beta 0 thal children) and beta thalassemia (beta thal) carriers identified during mass screening are reported. Red cell indices were similar in obligate beta 0 carriers and in carriers diagnosed during mass screening. However there was a higher incidence of anemia in female obligate beta 0 thal carriers. In Sardinia the beta 0 thal carrier showed the usual hematological characteristics of the high Hb A2 beta thal carrier with microcytosis, hypochromia, reduced osmotic fragility; Hb F greater than 1% was found in 30% of the carriers. With MCV, MCH, osmotic fragility test (OFT) and Shine and Lal discriminant function we found 3.5%, 1.5%, 3.5% and 4.0% respectively false negatives in carrier identification. A part from one subject, all obligate carriers had elevated Hb A2 levels. The alpha/beta ratio in obligate carriers (mean +/- SD) was 1.83 +/- 0.26 (N = 30).

Adolescent↗
PubMed1978

Hemoglobin H disease in Sardinia: phenotypic and genetic observations.

In this study the clinical and hematological characteristics, the transmission pattern and the relative rates of globin chain synthesis were determined in the members of four Sardinian families with 14 patients affected by hemoglobin H disease. The severity of hemoglobin H disease in Sardinian subjects shows a high degree of variability. Clinically it usually appears intermediate between the hemoglobin H disease found in Oriental and Negro populations. The alpha/beta specific activity ratio was 0.42 +/- 0.10 indicating an analogous biochemical defect like that described in the Chinese. On the basis of hematological data and alpha/beta ratio, the genetics of hemoglobin H disease in Sardinians seem to follow a pattern similar to that observed in Orientals: one parent showing alpha-thalassemia-1 trait and the other alpha-thalassemia-2 trait. Parent offspring transmission of hemoglobin H disease did occur in 2 out of 6 hemoglobin H matings with spouses carrying the alpha-thalassemia-1 gene. This observation indicates either a high frequency of alpha-thalassemia trait in Sardinians or a high incidence of inbreeding. In one family the mating of a patient with hemoglobin H disease and a normal person produces 6/6 offspring with alpha-thalassemia-1. The genetic implications of this transmission pattern are discussed.

Adult↗
PubMedDate not supplied

Haplotype and mutation analysis in Greek patients with Wilson disease.

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

[Determination of HbA2 by a microchromatographic method. Reliability and simplification of the use of prepared columns].

A modified procedure for hemoglobin A2 determination by microchromatography was developed simplifying an easily commercially available column kit method. Blood samples were analyzed simultaneously by means of DE-52 microchromatography described by Huisman et al. (reference 12) to check the reliability of the new modified method. In the Pediatric Clinic of Cagliari University where the original Huisman method was used the values of HbA2 obtained were as follows: Normal subjects (35 cases) 2.470 +/- 0.351, beta-Thalassemia heterozygous subjects (38 cases) 5.142 +/- 0.342. The modified method gave respectively the following results: Normal subjects 2.578 +/- 0.303, beta-Thalassemia heterozygous subjects 5.465 +/- 0.400. No overlap was found between normal and beta-thalassemia trait samples. It is suggested that the simplified method is very reliable and very simple to organize even in laboratories with few facilities and when needs for only few tests per week exist.

Child↗