Mild cystic fibrosis phenotype in patients with the 3272-26A > G mutation.
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Adolescent↗
Biomedical subjects
C Kattamis
Publications and source records attributed to C Kattamis.
Preliminary mutation analysis in the phenylalanine hydroxylase gene in Greek PKU and HPA patients.
The presence of nine mutations in the phenylalanine hydroxylase (PAH) gene, previously described in phenylketonuria (PKU) patients of other Mediterranean and European populations, was assessed in 47 Greek PKU and 3 hyperphenylalaninaemia (HPA) patients. Of the nine mutations investigated, only five were detected, characterizing 31% of the PKU alleles in our patients.
Alleles↗
The molecular basis of normal HbA2 (type 2) beta-thalassemia in Greece.
Heterozygotes for beta-thalassemia usually have raised levels of HbA2, but in Greece about 5% of beta-thalassemia carriers are observed to have normal or borderline levels. It is postulated that such cases have mild beta+ thalassemia mutations or coinheritance of delta-thalassemia. We selected 18 heterozygotes with the hematological phenotype of normal HbA2 (type 2) beta thalassemia who were negative for the delta beta Corfu mutation, and screened them for previously defined Mediterranean beta-thalassemia and delta-thalassemia mutations. The coinheritance of beta and delta-thalassemia was demonstrated in four cases with the following genotypes: in cis beta+ IVSII -n745/delta+ 27, beta 0NS39/delta 059(-A), beta+ IVSI-n110/delta 059(-A) and in trans beta+ IVSI-n6 and delta+ 27. A further nine heterozygotes had mild beta(+)-thalassemia mutations (eight with the beta+ IVSI-n6 mutation, one with the beta+ polyA (A-->G) mutation). In four heterozygotes with severe beta-thalassemia chromosomes (2 beta+ IVSI-n110, 1 beta 0 FSC-6, 1 beta 0 IVSI-n1) no known delta-thalassemia mutations were observed. One case had a delta beta deletion chromosome. These results indicate that the hematological phenotype of normal HbA2 (type 2) beta-thalassemia in Greece is genetically heterogeneous; it is mainly associated with the delta beta Corfu mutation or coinheritance of beta and delta thalassemia mutations or with very mild beta(+)-thalassemia mutations, mainly beta+ IVSI-n6. In the rare cases with severe beta-thalassemia mutations, the normal levels of HbA2 may be due to coinheritance of as yet undefined delta thalassemia mutations.
Base Sequence↗
Characterization of nondeletion alpha-thalassemia mutations in the Greek population.
alpha-Thalassemia is usually due to deletions within the alpha-globin gene cluster, leading to loss of function of one (-alpha) or both [-(alpha) or --] alpha-globin genes. Nondeletion mutations (denoted alpha alpha T or alpha T alpha) are less frequent and in Greece are not well defined. We report the analysis of 16 nondeletion alpha-thalassemia chromosomes using a polymerase chain reaction method to amplify specifically the alpha 2-globin gene, which was subsequently screened using ASO hybridization or restriction enzyme analysis for four mutations already characterized in other Mediterranean and Middle Eastern populations. Of the 16 nondeletion chromosomes, nine had the polyadenylation signal mutation (alpha PolyA alpha), two the IVSI 5' pentanucleotide deletion (alpha Hph alpha), two the Hb Icaria mutation (alpha Ic alpha), and one the initiation codon mutation (alpha Nco alpha). In two, the defects are still undefined. These findings show that nondeletion alpha-thalassemia in Greece is heterogeneous and that the most frequent mutation (accounting for > 50%) is the polyadenylation signal mutation, which to date was most commonly found in the Saudi Arabian population.
Alleles↗
Relapse of herpes simplex encephalitis after acyclovir therapy.
A case of herpes simplex encephalitis in a previously healthy 17-month-old girl relapsing 1 week after completion of a 10-day acyclovir therapy is described. The child responded favourably to a second 10-day course with acyclovir. The time of relapse and the satisfactory response to a second course of acyclovir treatment indicate that the first course of therapy was inadequate for eradication of herpes simplex virus infection.
Acyclovir↗
A base substitution (T-->C) in codon 29 of the alpha 2-globin gene causes alpha thalassaemia.
We have identified three individuals of Greek or Greek Cypriot origin with an atypical form of HbH disease characterized by a severe hypochromic microcytic anaemia associated with relatively small amounts of HbH in the peripheral blood. Molecular analysis has shown that each is a compound heterozygote for a previously described mutation affecting the poly A addition signal (AATAAA-->AATAAG) and a previously undescribed mutation involving a T-->C transition in codon 29 of the alpha 2 gene causing a leucine-->proline substitution. Although this mutation would be expected to produce an unstable haemoglobin and hence a haemolytic anaemia, simple heterozygotes for the alpha 29Leu-->Pro mutation have the phenotype of alpha-thalassaemia trait.
Adult↗
Flow-cytometric analysis of reticulocytes in normal cord blood.
We performed precise reticulocyte counts and a reticulocyte maturation study according to ribosomal RNA (rRNA) content, in normal cord blood. For this purpose we analyzed 35 cord blood specimens corresponding to a mean gestational age of 39.2 weeks (range 38-41). In all specimens complete blood counts were performed with the H*1 (Technicon, Bayer) analyzer. Reticulocyte maturation study and counts were conducted by the R-1000 (Sysmex) reticulocyte analyzer. We obtained the following measurements (mean +/- 1 SD): reticulocyte percentage 3.11 +/- 0.75% and reticulocyte absolute count 137.3 +/- 33.3 x 10(9)/l. There was no correlation between the reticulocyte counts and the duration of gestation or the type of labor (normal, forceps assisted or cesarean section). Reticulocyte subpopulations with different rRNA content and maturation were expressed as reticulocytes with high (HFR), median (MFR) and low (LFR) fluorescence of the fluorochrome auramine bound to rRNA. Normal cord values were: HFR% = 13.6 +/- 2.4, MFR% = 22.5 +/- 2.4 and LFR% = 63.9 +/- 4.3. Reference maturation subpopulations were assessed for comparison in 180 samples of healthy adults (90 males and 90 females) and were found HFR% = 1.0 +/- 0.8, MFR% = 9.7 +/- 3.3 and LFR% = 89.2 +/- 3.4. The HFR% and MFR% were significantly higher while LFR% was significantly lower (p < 0.001) in cord compared to adult blood, denoting a shift to more immature reticulocyte forms. The above values are provided as normal reference data of the reticulocyte maturation profile in full-term cord blood.
Adult↗
Correlation of in vitro enhancement of erythropoiesis and clinical response to steroids in Diamond-Blackfan anaemia.
To investigate whether the clinical response to steroids in Diamond-Blackfan anaemia (DBA) can be predicted in vitro, erythroid cultures from six patients was performed. The increment of burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) derived colonies had been studied with the in vitro addition of steroids. Our results showed: 1) a relative insensitivity to low and optimum concentration of erythropoietin (Epo) in cultures, and 2) lower CFU-E and BFU-E colony formation in all cases studied. (CFU-Es of normal controls/10(5) cells; were 85.6, BFU-Es 37.8, while the patients' CFU-E were 18.1 and BFU-E 7/10(5) cells with two IU of Epo) with poor or no growth in three cases, 3) increment up to 60-110% with in vitro addition of steroids in three cases, 4) high serum Epo levels in all Diamond-Blackfan anaemia patients, and 5) clinical response to steroids in the three patients who responded in vitro.
Adult↗
A new delta chain variant hemoglobin A2-Corfu or alpha 2 delta 2 116 Arg----Cys (G18), detected by delta-globin gene analysis in a Greek family.
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Amino Acid Sequence↗
The Corfu delta beta thalassaemia mutation in Greece: haematological phenotype and prevalence.
The Corfu delta beta thalassaemia mutation, a 7.2 kb deletion partially removing the delta-globin gene and a single nucleotide mutation (G----A) at intervening sequence I (IVSI-n5) in the beta-globin gene in cis, was first described in a family from Corfu; the carriers for this mutation had the unusual haematological phenotype of heterozygous beta-thalassaemia with normal levels of HbA2. To investigate the frequency and haematological characteristics of Corfu delta beta thalassaemia in Greece we analysed 25 unrelated normal HbA2 type 2 beta-thalassaemia heterozygotes and their 23 clinically affected offspring. Gene mapping demonstrated that nine (36%) of the 25 normal HbA2 beta-thalassaemia heterozygotes were in fact Corfu delta beta thalassaemia heterozygotes and of the 23 patients, two were Corfu delta beta thalassaemia homozygotes and five compound heterozygotes for Corfu delta beta thalassaemia and another beta-thalassaemia defect. Detailed haematological analysis demonstrated that: the Corfu delta beta thalassaemia mutation does not completely abolish the expression of the beta-globin gene; the HbA2 levels are slightly lower (P less than 0.01) and the HbF levels slightly higher (P less than 0.01) in Corfu delta beta thalassaemia heterozygotes compared to beta-thalassaemia heterozygotes with the normal HbA2-type 2 phenotype who do not have the Corfu delta beta chromosome.
Chromosome Deletion↗
Serum erythropoietin in regularly transfused thalassemic patients.
Serum erythropoietin levels were measured in 67 regularly transfused thalassemic patients with pre-transfusion hematocrit ranging from 25-32% and in 40 normal individuals. In patients, mean erythropoietin levels were slightly increased (mean 91.5 miu/ml) as compared to normal individuals (mean 42 miu/ml). The distribution of erythropoietin (Ep) was wide in thalassemic patients. 40% had normal or decreased and 60% increased Ep levels. A reverse relation between pretransfusion Hct and erythropoietin activity was observed only among patients with normal erythropoietin levels and splenectomized patients with high erythropoietin titers suggesting that a normal feedback between tissue hypoxia and erythropoietin activity occurs in these groups. The effect of regular blood transfusions in reversing tissue hypoxia resulting from anemia in the majority of regularly transfused thalassemic patients seems to be satisfactory, as it is assessed by serum erythropoietin levels.
Adolescent↗
Molecular basis of delta beta-thalassemia with normal fetal hemoglobin level.
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Fetal Hemoglobin↗
A multi-level intervention approach for care of HIV-positive haemophiliac and thalassaemic patients and their families.
The experience gained from the application of an on-going multilevel intervention programme through an interdisciplinary team approach to the management of 30 HIV-positive children, adolescents and young people aged from 7 to 21 years (20 haemophiliac and 10 thalassaemic patients) and their families is described. The objective of the intervention was to assess the family's needs, to help parents and other family members to contain the anxiety of seropositive children and to improve their interraction with the family as well as with others in their social environment. The intervention was also designed to help family members to cope with their grief. Work with the medical and nursing staff, on the other hand, was intended to increase their understanding of the emotions caused in them by occupational stress, such as fear, anxiety, prejudice and feelings of guilt related to the iatrogenous nature of the infection. The need for follow-up studies is stressed to allow assessment of the effectiveness of the intervention and to search for protective factors, successful coping skills, strategies and adaptational resources.
Adaptation, Psychological↗
Molecular characterization of beta-thalassaemia in 174 Greek patients with thalassaemia major.
The mutations producing beta-thalassaemia in 174 Greek patients with thalassaemia major were investigated by dot-blot hybridization of oligonucleotide probes to genomic DNA amplified by the polymerase chain reaction procedure, by direct sequencing of amplified DNA, and by gene mapping. beta-thalassaemia in Greeks was found to be very heterogeneous at the molecular level as 17 different mutations were observed: 86.6% of the beta-thalassaemic genes, however, could be identified with five probes: IVS-I-110 (G----A) (42.5%), codon 39 (C----T) (17%), IVS-I-1 (G----A) (13.2%), IVS-I-6 (T----C) (7.2%) and IVS-II-745 (C----G) (6.9%). Several mutations which had not previously been reported in the Greek population and which occurred at an incidence of 2% or lower were observed in this study. The information obtained will facilitate the prenatal diagnosis of beta-thalassaemia in Greece.
Adolescent↗
Two novel polyadenylation mutations leading to beta(+)-thalassemia.
In an ongoing effort to identify point mutations causing beta-thalassaemia, we have found two previously unreported mutations which are located in the Poly A site of the beta-globin gene. The screening programme used amplified DNA and dot-blot hybridization with several 32P-labelled oligonucleotide probes. DNA samples which remained unidentified by this methodology were subjected to sequencing with 32P-labelled primers and modified T7 DNA polymerase. The newly discovered mutations were confirmed by the dot-blot hybridization technique. One type concerned an AATAAA----AATGAA mutation in the polyadenylation site and was found in one family from Yugoslavia (including one patient with the C----T mutation at codon 29 in trans), one from Bulgaria (the patient had the G----A mutation at IVS-I-110 in trans), and one from Greece (this patient had the C----G mutation at IVS-II-745 in trans). Haematological data for three simple heterozygotes suggested a rather mild beta(+)-thalassemia. The second type involved an AATAAA----AATAGA mutation and was found in one family from Malaysia. The propositus had the beta E mutation on the other chromosome, was originally diagnosed as mild Hb E-beta(+)-thalassaemia, and had Hb A and Hb E percentages which were nearly the same.
Adult↗
Red cell alloantibodies in patients with thalassemia.
We present the results of tests carried out to detect alloimmunization against red cells in 1,200 patients (607 males and 593 females), transfused and followed up during the period 1981-1987 in our hospital. Of these patients, 1,135 were thalassemic and 65 had sickle cell/beta-thalassemia. In 162 patients who received blood matched for the AB0, rhesus and Kell systems from their first transfusion, the immunization rate was very low (3.7%). In a pilot group consisting of 83 patients with the same clinical characteristics, who received blood matched only for the AB0 and Rh-D antigens, there was a significant difference in the frequency of alloantibodies (15.7%, p less than 0.001). Of 1,038 patients who received blood only matched for AB0 and Rh-D 244 (23.5%) with one or more red cell alloantibodies were identified. Of these 1,038 patients, 973 were exclusively thalassemic. In 220 (22.6%) of them, alloantibodies were found. The sickle cell beta-thalassemia patients presented alloantibodies with a higher frequency (36.9%, 24/65). Only one antibody was found in 114 patients (51.8%) and two or more in 106 patients (48.2%). The alloimmunization significantly concerned the rhesus (34.0%) and Kell (29.8%) systems. Anti-Kell was most often identified (28.5%). Alloimmunization appears considerably lower in patients in whom blood transfusion is started before the age of 3 than in those in whom it is started after that age (20.9 vs. 47.5%, p less than 0.0001).
Adolescent↗
Growth and development in children with thalassaemia major.
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Adolescent↗
Experience of splenectomy and cholecystectomy in children with chronic haemolytic anaemia.
Since 1973, 419 children (233 boys, 186 girls) with chronic haemolytic anaemia (mean age, 10.2 +/- 3.5 years) have been splenectomised. Fifty-three (12.6%) have also been cholecystectomised because of cholelithiasis. Between 1973 and 1982, cholecystectomy and splenectomy were performed at the same time in symptomatic patients. Later, between 1983 and 1987, cholecystectomy was also performed in clinically asymptomatic patients with positive sonographic findings. In the first period, 11 thalassaemic patients (45.8%) were cholecystectomised a short period after splenectomy (in two cases, only 2 and 3 weeks later). Between 1983 and 1987, when asymptomatic patients with cholelithiasis were screened by sonography, simultaneous cholecystectomy and splenectomy were performed in 13.6% of the patients with thalassaemia, in 41% of the patients with sickle cell or microdrepanocytic disease, and in 22.2% of the patients with spherocytosis. As there is a high incidence of asymptomatic cholelithiasis and hypersplenism in patients with chronic haemolytic anaemia, screening for gallstones should precede splenectomy. Simultaneous cholecystectomy should be performed in patients with cholelithiasis.
Adolescent↗