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Biomedical subjects

C Altay

Publications and source records attributed to C Altay.

At least 55 records · Page 3Linked to original sources
PubMed1991

The G----A mutation at position +22 3' to the Cap site of the beta-globin gene as a possible cause for a beta-thalassemia.

We describe the occurrence of a chromosome with a G----A mutation at position +22 relative to the Cap site that was found in five patients with beta-thalassemia. All patients had a common type of beta-thalassemia mutation on the second chromosome, namely the frameshift at codon 8 (-AA), the IVS-I-110 (G----A) and the IVS-II-1 (G----A) mutations. The beta genes of two patients, including the 5' and 3' untranslated regions, were completely sequenced and no other mutations, except a few polymorphic sites, were observed. Dot-blot analyses failed to demonstrate this G----A mutation at +22 in nearly 400 beta-thalassemia chromosomes and 180 normal chromosomes. Heterozygotes have the features of a high Hb A2-beta-thalassemia heterozygosity, although the hematological parameters might be less abnormal than observed in heterozygotes for the more common beta-thalassemia mutations. The possibility has been presented suggesting that this mutation might impair the binding of mRNA to ribosomes. Another mutation in this segment of DNA, i.e. a C----G mutation at position +20, is observed exclusively on a chromosome which also carries the C----G mutation at IVS-II-745. It is postulated that the +20 C----G mutation accentuates the beta-thalassemia condition caused by the IVS-II-745 mutation; the mechanism might be similar to that suggested for the G----A at +22 mutation.

Alleles↗
PubMed1990

Variation in the level of fetal hemoglobin in (delta beta) (0)-thalassemia heterozygotes with different numbers of alpha-globin genes.

The Sicilian type of (delta beta) (0)-thalassemia characterized by a approximately 13 kb deletion, was present in a Turkish boy who is a homozygote and in his heterozygous parents who are first cousins. The father with approximately 21% Hb F had five alpha-globin genes (alpha alpha/alpha alpha alpha) and the mother with approximately 10% Hb F had an alpha-thal-2 heterozygosity (alpha alpha/-alpha). The difference in Hb F level is explained by a decreased formation of alpha 2 gamma 2 tetramers in the mother with an alpha-chain deficiency while the extra alpha-globin gene in the father will promote Hb F production.

Child, Preschool↗
PubMed1990

Beta-thalassemia intermedia in Turkey.

DNA data have been collected for 41 patients with beta-thalassemia intermedia without transfusion dependency. They belonged to 33 families, and 45 of their parents were included in the study. Eight patients were homozygous for the frameshift at codon 8 (-AA), and nine were homozygous for the IVS-2 nt 1 (G----A) mutation; haplotypes IV and III, respectively, were associated with these mutations. Three patients had a G gamma A gamma(delta beta)0-thalassemia homozygosity, characterized by a deletion of 13 kb. Of the remaining subjects, ten had a homozygosity for the IVS-1 nt 6 (T----C) mutation, and five were compound heterozygotes for one mild and one severe thalassemia determinant. Combinations with Hb Knossos, the T----A mutation at nt -30, the C----T mutation at nt -101, the G----A and G----C mutations at IVS-1 nt 5, and the G----A mutation at IVS-1 nt 110 were the other thalassemia determinants resulting in beta-thalassemia intermedia in the six remaining patients. Haplotypes IV and IX were associated with the latter three mutations. The C----T mutation at nt -158 5' to the G gamma gene was characteristic for haplotypes III, IV, and IX. Genotype and phenotype correlation indicated significant differences in some of the hematological parameters among patients with the frameshift at codon 8 (-AA) or with the IVS-2 nt 1 (G----A) mutation, with both the frameshift at codon 8 and the T----C mutation at IVS-1 nt 6, and with both the IVS-2 nt 1 (G----A) and IVS-1 nt 6 (T----C) mutations. Statistically significant differences were found in the mean values for hemoglobin (Hb) A2 in heterozygotes with the frameshift at codon 8 (-AA) and the IVS-1 nt 5 (G----A) mutation. Variations in the number of alpha-globin genes resulted in modifications of the phenotypical expression of the beta-thalassemia intermedia determinants.

Chromosome Deletion↗
PubMed1990

Beta-thalassemia in Turkey.

A review is presented of the various beta-thalassemia alleles observed in nearly 191 patients with beta-thalassemia major and their 182 heterozygous relatives. Determination was by gene amplification and dot-blot hybridization with synthetic probes, specific for 27 different mutations. Eighteen mutations have been observed; six of these account for nearly 83% of all thalassemia abnormalities. A new mutation, i.e. a G----C mutation at the acceptor splice site of IVS-I, was found in one teenager who was homozygous for this disease. The high consanguinity among the families was considered the main reason for the high number of patients with a homozygosity for the IVS-I-110 (G----A) mutation. Combinations of different mutations were present in many patients; some were mildly affected because of the specific mutation present on one chromosome. Combinations of classical beta-thalassemia and an abnormal hemoglobin mainly concerned Hb S. Hbs Knossos and Lepore were rare occurrences. A comparison of hematological data for adults with heterozygosities for some of the common alleles confirmed the low Hb A2 values in IVS-I-6 (T----C) heterozygotes and the high Hb F values for codon 8 (-AA), IVS-II-1 (G----A), and IVS-I-1 (G----A) heterozygotes.

Adolescent↗
PubMed1989

A C----T substitution at nt--101 in a conserved DNA sequence of the promotor region of the beta-globin gene is associated with "silent" beta-thalassemia.

Sequence analyses and dot-blot analyses with synthetic oligonucleotide probes have identified eight individuals in three Turkish families and one Bulgarian family with one chromosome having a C----T mutation at nucleotide position--101 relative to the Cap site of the beta-globin gene. This nucleotide is part of one of the conserved blocks of nucleotides within the promoter region; in vitro expression analyses with the chloramphenicol acetyltransferase system showed that this substitution will decrease the effectiveness of transcription. Five subjects had a thalassemia intermedia due to the additional presence of a known classical high hemoglobin (Hb) A2 beta-thalassemia mutation on the second chromosome; their hematologic condition was relatively mild. The three persons with a heterozygosity for the--101 C----T mutation had normal hematologic data without microcytosis but with high-normal levels of Hb A2 and a mild imbalance in chain synthesis. The newly discovered mutation is considered one of the silent types of beta-thalassemia. It is relatively rare because it was absent among several hundred normal and beta-thalassemia chromosomes.

Base Sequence↗
PubMed1989

The levels of zeta, gamma, and delta chains in patients with Hb H disease.

Details are given of a study of blood samples from 24 patients with Hb H disease from different Mediterranean countries and from the Far East. Four different types of alpha-thal-1 (--) were observed, namely -(alpha) (approximately 20.5-kb deletion); --MED-I (approximately 17.5-kb deletion); --MED-II (greater than 26.5-kb deletion); and --SEA (approximately 18-kb deletion, in Orientals only). The alpha-thal-2 was mainly of the deletion type (16 with the 3.7-kb deletion; 1 with the 4.2-kb deletion), while 4 of the 7 patients with a nondeletional type had the five-nucleotide deletion at the donor splice site of the first intron of the alpha 2 gene. All patients had a mild-to-moderate hemolytic anemia; no significant differences in hematology were observed between the groups. Hb A2 was decreased to about one-third of the normal level. The Hb H formation varied considerably and its quantitation was not always satisfactory. Patients with Hb H disease due to any alpha-thal-1 combined with a nondeletional alpha-thal-2 had the highest Hb H levels and a more marked anemia. The zeta chain production was small and absent in patients with the MED-II type of alpha-thal-1 because this deletion included the zeta and psi zeta genes. The highest zeta chain levels were present in the four patients with the SEA type of alpha-thal-1. The gamma chain production was increased, particularly in patients with a mutation of C----T at position -158 to the G gamma globin gene. This gamma chain was primarily present as Hb Bart's (or gamma 4) and only about 15% was recovered as Hb F or alpha 2 gamma 2. The evaluation of the rate of gamma chains produced in these patients was greatly facilitated by data from one patient who had Hb H disease and a heterozygosity for the A gamma-beta+-HPFH. The low levels of Hb A2 and of Hb F (relative to Hb Bart's) can be explained by a decreased affinity of alpha chains for delta and gamma chains as compared with beta chains in conditions of severe alpha chain deficiency.

Adolescent↗
PubMed1989

Role of protein C in childhood cerebrovascular occlusive accidents.

A group of 23 children with cerebrovascular occlusion of unknown etiology were re-evaluated 6 months-2 years later. Plasma protein C levels were determined with the coagulation method and were low in 10 cases. The role of this deficiency and the necessity of this test in cerebrovascular occlusion is discussed.

Adolescent↗
PubMed1989

Molecular heterogeneity of beta-thalassemia intermedia in Turkey.

A total of 38 patients with beta-thalassemia intermedia from 30 families were were studied. Twelve of the thirty unrelated patients had beta zero-thalassemia which was due to a homozygosity for one of two different thalassemia defects, namely the frameshift at codon 8, and the IVS-II-1 G----A mutation. Another mild variation, a beta +-thalassemia, was a homozygosity for the mutation of T----C at position 6 of IVS-1 (10 patients). Compound heterozygosities for mild thalassemic determinants or for one mild and one severe beta-thalassemic determinant were also found in some patients with beta-thalassemia intermedia. The mutations at beta-39 and IVS-I-110 were the most commonly occurring thalassemic determinants in these patients. Correlations between genotype and phenotype indicated significant differences in some of the hematological parameters among patients with the IVS-I-6 and the frameshift at codon 8, IVS-I-6 and IVS-II-1, and the frameshift at codon 8 and IVS-II-1 mutations.

Adolescent↗
PubMed1989

Beta-thalassemia intermedia in two Turkish families is caused by the interaction of Hb Knossos [beta 27(B9)Ala----Ser] and of Hb City of Hope [beta 69(E13)Gly----ser] with beta (0)-thalassemia.

We have studied a few members of two Turkish families, who had a beta-thalassemia of the intermediate type. An abnormal hemoglobin was found in both families, which when present in association with beta(0)-thalassemia was considered to be the primary cause for the increased severity of the disease. In the first family this variant was Hb Knossos [beta 27(B9)Ala----Ser] which occurred together with the frameshift in codon #8 type of beta(0)-thalassemia. This compound heterozygosity, observed for the first time in the Turkish population was characterized by a considerable increase in Hb F production, mainly of the G gamma type, as expected for a chromosome with haplotype IV. In the second family, the variant was Hb City of Hope [beta 69(E13)Gly----Ser] which was present in combination with an unknown type of beta-thalassemia. The increase in Hb F production in the compound heterozygote was minimal. Reversed phase high performance liquid chromatography and the DNA amplification-synthetic oligonucleotide probe procedure were major tools in identifying the different abnormalities.

Adult↗
PubMed1989

A search for anomalies in the zeta, alpha, beta, and gamma globin gene arrangements in normal black, Italian, Turkish, and Spanish newborns.

Globin gene mapping analyses of DNA from numerous Black babies, and from newborns from Sardinia, Sicily, Turkey, and Spain have identified the following: A high incidence of alpha-thalassemia-2 heterozygotes among Black babies with less than 1% Hb Bart's at birth and a high incidence of alpha-thalassemia-2 among Sardinians, but not among Sicilian, Turkish, and Spanish babies. A relatively high incidence of zeta-thalassemia was present among Black babies only, while triplicated zeta was seen in four of the five populations. Two Black babies were each found to have a different theta 1 deletion; two Sardinian babies had a newly discovered approximately 2.5 kb deletion between zeta and psi zeta; four babies had the rare Bgl II polymorphism between psi zeta and psi alpha; and one Black baby lacked the Eco RI site 3' to zeta. Quantitation of the zeta chain by reversed phase high performance liquid chromatography showed that two-thirds of the babies with four alpha genes (alpha alpha/alpha alpha) had levels between 0.1 and 1.0%, while nearly 90% of the babies with -alpha/alpha alpha had similar levels (averaging 0.2% for alpha alpha/alpha alpha; 0.35% for -alpha/alpha alpha; 0.75% for -alpha/-alpha). Additional data indicated that the occurrence and level of zeta are related to the level of beta, i.e. the gestational age. The presence of a zeta triplication did not affect the level of zeta in cord blood. The extensive search for gamma-globin gene anomalies resulted in the discovery of a chromosome with five gamma genes. gamma-Thalassemia was rare in all populations, while the -G gamma-G gamma- gene arrangement was mainly observed among Black babies; this arrangement is primarily responsible for high G gamma levels in cord blood samples. The strong correlation between the presence or absence of a C----T mutation at position -158 (measured in Xmn I digests) and the level of G gamma was confirmed for adult blood samples. A search for possible anomalies in the -delta-beta- region through gene mapping with Eco RV gave negative results except for the discovery of a polymorphic site 5' to delta in one of the 371 Black babies tested.

Black People↗
PubMed1989

An A gamma type of nondeletional hereditary persistence of fetal hemoglobin with a T----C mutation at position -175 to the cap site of the A gamma globin gene.

The nondeletional types of hereditary persistence of fetal hemoglobin (ndHPFH) concern the continued synthesis of hemoglobin (Hb) F with either G gamma or A gamma chains in amounts varying from 5% to 30%. Several mutations have been identified in either the A gamma or G gamma promoter which are considered causative to the continued production of one of the two gamma chains because the substitutions occur in sequence motifs essential for the expression characteristics of the gamma-globin gene in the 3' position. We report the discovery of a T----C mutation at position -175 in the A gamma promoter which was associated with a greatly increased level of Hb F (with mainly A gamma) and a decreased level of Hb A in the one (Black) heterozygote who had a beta c gene in trans. The same mutation has been observed in the G gamma promoter of a Black heterozygote who had high levels of Hb F with G gamma chains only. A detailed comparison between these two individuals indicated significant differences in the levels of Hb F and Hb A which may result from an additional mutation at position -158 in the G gamma promoter.

Adult↗
PubMed1988

Beta-thalassemia due to a T----A mutation within the ATA box.

Sequence analyses of amplified DNA from a Yugoslavian patient with Hb Lepore-beta-thalassemia and from his father with a simple beta-thalassemia trait have revealed a T----A mutation within the ATA box at a position 30 base pairs upstream from the Cap site. The nucleotide substitution was confirmed through dot-blot analysis of amplified DNA with specific 32P-labeled synthetic oligonucleotide probes. The patient had a clinically severe condition; his Hb Lepore-beta-thalassemia was of the beta + type, as about 8-10% of the non-alpha chain was normal beta A. The same T----A mutation at nucleotide -30 was present on both chromosomes of a young Turkish patient who suffered from a thalassemia intermedia with a low level of Hb F (13.1%) and a relatively high beta A chain synthesis. These data are similar to those obtained for other types of beta +-thalassemia caused by comparable substitutions at positions 31, 29, and 28 base pairs upstream from the Cap site of the beta-globin gene.

Base Sequence↗
PubMed1988

Poor prognosis in children with acute nonlymphoblastic leukemia in Turkey.

Two hundred fourteen children with acute nonlymphoblastic leukemia (ANLL) were diagnosed between July 1975 to January 1987 in our center. Only 106 (50%) of the children could be treated. An initial hematologic remission was attained in 61 (58%) with a median duration of hematologic remission of 7.5 months and median survival of 12 months. Five patients who completed 36 months of therapy are still in initial remission, less than or equal to 84 months. Exophthalmos at presentation, which is clearly related to shorter duration of remission, was observed in 11% of these children. In two cases, it was the first sign of leukemia, 6 and 7 months prior to obvious bone marrow involvement. Twenty percent of the 61 patients who achieved remission discontinued their chemotherapy during the course of treatment while they were in remission, which indicates a different problem in the treatment of these patients in Turkey. Despite administration of similar treatment protocols, the prognosis of our patients was worse than the results observed in developed countries. We conclude that poor socioeconomic and nutritional conditions should also be considered among the high-risk factors for children with ANLL, as experienced in our patients with acute lymphoblastic leukemia (ALL).

Adolescent↗
PubMed1988

High levels of lactate, pyruvate, and alanine in anemic children.

Lactate, pyruvate, and alanine levels were investigated in patients with iron deficiency anemia and other types of anemia. The study was carried out on 36 children between 2 and 16 years of age. The study group was divided into three groups, each comprised of 12 children. It was shown that the anemic children have lower PO2, higher PCO2 and higher levels of lactate, pyruvate, and alanine than the control group (p less than 0.05). There was a negative linear correlation between lactate levels and hemoglobin values (r = -0.6213; p less than 0.05), but no correlation between hemoglobin and the alanine and pyruvate levels. Levels of lactate, pyruvate and alanine were similar in the iron deficiency and the other anemia groups. In conclusion, iron has no direct effect on the levels of lactate, pyruvate, and alanine, but the hypoxemia caused by anemia could be responsible for the higher levels of the lactate, pyruvate, and alanine. In cases with high levels of lactate, pyruvate, and alanine, anemia has to be considered in the differential diagnosis of hyperlactatemia.

Adolescent↗
PubMed1988

Mild and severe beta-thalassemia among homozygotes from Turkey: identification of the types by hybridization of amplified DNA with synthetic probes.

Through the procedure of gene amplification combined with hybridization to synthetic 19 base pair (bp) oligonucleotide probes, it has been possible to identify nine different mutations in the DNA of 47 subjects from Turkey and Northern Cyprus with a beta-thalassemia homozygosity. The IVS-I nucleotide (nt) 110 G----A and the IVS-I nt 6 T----C substitutions and the frameshift at codon 8 were most frequently observed. Direct correlations were made between these data and clinical observations; mild disease was associated with homozygosity for IVS-I nt 6 T----C, for frameshift at codon 8, for the C----G substitution at nt -87, and for IVS-I nt 5 G----T, and for a double heterozygosity for some of these conditions. Moderate disease, observed in some of the patients, could be explained by combinations of specific mutations. All mutations were associated with specific haplotypes, while in some the observed beta zero-thalassemia was of the mild type due to a considerable production of Hb F.

DNA↗