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Biomedical subjects

C Altay

Publications and source records attributed to C Altay.

At least 37 records · Page 2Linked to original sources
PubMed1999

Variable pathogenicity of exon 43del (FAA) in four Fanconi anaemia patients within a consanguineous family.

Four Fanconi anaemia group A (FAA) patients within two related consanguineous families are presented: the propositus (male, 13 years, transplanted at age 10), and his three cousins (one male, 8 years, and two female newborns). Assignment of the patients to FAA was based on the functional complementation analysis by somatic cell hybridization and confirmed by mutation screening showing a homozygous deletion of exon 43 (4267-4404del) in the FAA gene to be present in all four patients. The newborn patients had been diagnosed prenatally by DNA analysis. In spite of identical molecular pathology and close familial relationship the clinical phenotypes of the four patients were not concordant. Discordant symptoms included birthweight, pigmentation abnormalities, skeletal, renal and genital abnormalities, whereas microcephaly and possibly the haematological course were concordant. Differences in environmental conditions and/or genetic make-up along with chance effects during development may explain discordant phenotypes despite identical molecular pathology in these patients. However, our results do not rule out the possibility that the exon 43del mutation may have prognostic value for the haematological course of the disease.

Adolescent↗
PubMed1999

Transferrin receptor on peripheral blood lymphocytes in iron deficiency anaemia.

The effect of iron deficiency anaemia (IDA) on CD71 expression by peripheral blood lymphocytes was studied in 43 children with iron deficiency anaemia. 18 healthy age-matched children were selected as the control group. 11 children with beta-thalassaemia trait were also studied. Lymphocytes bearing CD71 were enumerated by flow cytometric analysis of peripheral blood. At diagnosis, CD71+ peripheral lymphocytes (mean+/-SE) was 5.90+/-0-76% in patients with IDA and 12.60+/-0.98% in healthy controls (P=0.000). In beta-thalassaemia trait patients the peripheral blood CD71+ lymphocytes were 7.80+/-1.20%. In IDA patients there was a statistically significant correlation between the levels of CD71+ peripheral lymphocytes and haemoglobin value (P = 0.000). In 19 patients studied at days 0 and 30 of oral iron therapy, the number of peripheral blood CD71+ lymphocytes was shown to be increased from 5.90+/-0.76% to 12.11+/-1.21%. In severe IDA presence of a limited number of CD71+ peripheral blood lymphocytes indicated that severe IDA should be borne in mind when considering conditions responsible for the suppression of lymphocyte proliferation.

Adolescent↗
PubMed1999

The Fanconi anemia group E gene, FANCE, maps to chromosome 6p.

Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive disease with bone marrow failure and predisposition to cancer as major features, often accompanied by developmental anomalies. The cells of patients with FA are hypersensitive to DNA cross-linking agents in terms of cell survival and chromosomal breakage. Of the eight complementation groups (FA-A to FA-H) distinguished thus far by cell fusion studies, the genes for three-FANCA, FANCC, and FANCG-have been identified, and the FANCD gene has been localized to chromosome 3p22-26. We report here the use of homozygosity mapping and genetic linkage analysis to map a fifth distinct genetic locus for FA. DNA from three families was assigned to group FA-E by cell fusion and complementation analysis and was then used to localize the FANCE gene to chromosome 6p21-22 in an 18.2-cM region flanked by markers D6S422 and D6S1610. This study shows that data from even a small number of families can be successfully used to map a gene for a genetically heterogeneous disorder.

Cell Fusion↗
PubMed1998

Allogeneic bone marrow transplantation in Fanconi anemia from Turkey: a report of four cases.

Bone marrow transplantation (BMT) is currently the treatment of choice for patients with Fanconi anemia (FA) if a suitable donor is available. Four children with FA underwent allogeneic BMT from HLA-identical siblings during the period from 1995 to 1996. Pretransplant conditioning was Cyclophosphamide (Cy) (20 mg/kg) + Thoracoabdominal irradiation (TAI) (500 cGy) +/- Antithymocyte globulin (ATG) (2 mg/kg/day x 3). Cyclosporin A (CsA) was used as GvHD prophylaxis. The time of neutrophil (ANC>500) and platelet (>50,000) recovery were at 11-14 and 17-25 days, respectively. One patient with a pretransplant history of multiple transfusions experienced graft rejection and died at day +29 with infection and bleeding. Although three patients sustained engraftment one developed donor originated acute lymphoblastic leukemia (ALL) 18 months after BMT and died with CNS hemorrhage and infection at +25 months following 7 months of chemotherapy. None of the patients developed grade 3-4 acute GvHD. Cytotoxicity included grade II mucositis in all and severe gastroenteritis in one patient. During a follow-up period of 10 months and 2 years, two patients are well with normal blood count, recovering immune function and have a Karnofsky score of 90%.

Adolescent↗
PubMed1997

Molecular analysis of the Turkish form of deletion-inversion (delta beta)(0) thalassaemia.

Two unrelated (delta beta)(0)-thalassaemia patients from Southern Turkey are presented. DNA studies indicated that both of them are homozygous for the Turkish type of (delta beta)(0)-thalassaemia characterized by one large deletion of 11.5 kb including the delta and beta globin genes at the 5' end and one small deletion of 1.6 kb at the 3' end, which are separated by an inverted 7.6 kb long DNA segment that includes L1 repetitive sequence. In the present study a PCR-based method was performed to produce a unique deletion-specific product and subjected to sequence analysis for the determination of the breakpoint. DNA polymorphisms in the beta-globin gene cluster of deletion-inversion type of (delta beta)(0)-thalassaemia, IVS-I-6 and beta-39 globin genes were examined. Analysis of sequence variations in regulatory regions including the 5' hypersensitive site-2 of the locus control region (LCR), the delta, (G)gamma and (A)gamma 5' flanking regions and the second intervening sequence (IVS-II) of (A)gamma and (G)gamma genes indicated the presence of close similarities between the chromosome carrying the Turkish form of deletion-inversion (delta beta)(0)-thalassaemia and the chromosome associated with beta-39 nonsense mutation in haplotype II. These two chromosomes are characterized by the presence of a 4 base pair deletion in the (A)gamma(T) globin gene promoter. A C --> T alteration at position -199 5' to the delta gene was also found to be associated with the Turkish type of (delta beta)(0)-thalassaemia and beta-39 chromosome.

Adult↗
PubMed1997

Analysis of 65 Turkish patients with congenital aplastic anemia (Fanconi anemia and non-Fanconi anemia): Hacettepe experience.

During the last 14 years, 65 unrelated patients were diagnosed as having constitutional aplastic anemia (CAA). In 52 of 65 patients the diepoxybutane (DEB) test was positive. Comparison of several hematological and clinical parameters in Fanconi anemia (FA) (DEB+) and non-Fanconi anemia (non-FA)(DEB ) patients disclosed no statistically significant differences. The study indicated that in Turkey there were no peculiarities in associated congenital abnormalities in FA and non-FA. The rate of consanguinity was 78% in FA and 46% in non-FA, suggesting that also among the non-FA group recessively inherited disorders are hidden. The mean age at diagnosis in FA was 7.7+/-4.4 (1.8-12) and in non-FA 7.8+/-3.8 (2-15) years. Nine out of 52 FA and five out of 13 non-FA patients died during the follow-up period. Five of the 52 FA patients developed malignancies, three of them had acute myeloblastic leukemia (AML), one a squamous cell carcinoma of the gingiva, and another a hepatocellular carcinoma. Peliosis hepatica occurred in three of the FA and one of the non-FA patients. A total of seven patients stayed in remission without any medication. The remaining 58 patients were given 2-5 mg/kg of oxymetholone and 5 mg prednisolone treatment. Because of sustained remission, oxymetholone therapy was terminated in four of the 45 FA and two of the 13 non-FA patients. Detailed examination of the pedigrees of all of patients indicated the presence of multiple congenital anomalies. In seven of 52 FA and one of 13 non-FA patients there was increased risk for AML and/or other cancers among family members.

Abnormalities, Multiple↗
PubMed1997

The molecular basis of Hb H disease in Turkey.

A total of 25 unrelated Hb H patients were studied at the DNA level. Ten different genotypes were found to be responsible for the disease. The most prevalent alpha-thalassemia-2 determinant was the alpha alpha/-alpha (3.7) kb deletion (56%) which was followed by a nondeletional type of alpha-thalassemia, namely the pentanucleotide deletion in the 5' first intervening sequence splice junction [alpha(-5nt) alpha] (16%). The two most frequent alpha-thalassemia-1 determinants were alpha alpha/-20.5 kb and alpha alpha/-17.5 kb (MED-I) deletions. In two patients, homozygosity for the polyadenylation signal mutation [alpha (PA-2)alpha] was found to be responsible for Hb H disease. Clinical and hematological expression seems more severe in patients with the alpha (-5nt) alpha deletion at the donor site of the first intervening sequence and the alpha(PA-2) alpha mutation in trans to an alpha-thalassemia-1 determinant. Homozygosity for the alpha (PA-2)alpha mutation was also found to be associated with severe phenotype.

Adolescent↗
PubMed1996

The relative levels of alpha 2-, alpha 1-, and zeta-mRNA in HB H patients with different deletional and nondeletional alpha-thalassemia determinants.

We have analyzed the alpha 2/alpha 1-, alpha/beta-, zeta/(alpha + zeta)-mRNA ratios in the retic-ulocytes of 40 patients with Hb H disease. 21 patients had deletional Hb H disease (- -/- alpha), namely combinations of one of four types of alpha-thal-1 (MED-I, MED-II, -(alpha)20.5, SEA) and one of two types of alpha-thal-2 (-3.7 or -4.2 kb); 13 had Hb H disease because of combinations of one of these alpha-thal-1 deletions with either a 5 nt deletion at the 5' splicing site of IVS-I, or a terminating codon mutation (Hb CS), or a poly(A) mutation, and six were homozygous for either a poly(A) mutation or the 5 nt deletion. Significant differences were observed between the deletional types (- -/- alpha; alpha 2/alpha 1 ratio of zero; alpha/beta ratio of approximately 1) and non-deletional types (- -/alpha T alpha; alpha 2/alpha 1 ratio of 0.05-0.3 for those with T = the 5 nt deletion or the terminating codon mutant, and approximately 1.0 for those with T = a poly(A) mutation; alpha/beta ratio in all types of approximately 0.7). Comparable data were found for the nondeletional alpha-thal-2 homozygotes. The noted differences were highly significant and the determination of the two ratios may be diagnostically of considerable value. The low alpha 2/alpha 1-mRNA ratio in the two patients with - -/alpha-5nt alpha and the one patient with alpha-5nt alpha/alpha-5nt alpha indicates the presence of minute amounts of alpha 2-mRNA; apparently splicing at the donor site is greatly impaired by this deletion but not eliminated. The high alpha 2/alpha 1-mRNA ratio in the four patients with - -/alpha PA-2 alpha and the five patients with alpha PA-1 alpha/ alpha PA-1 alpha (PA-1 and PA-2 are poly(A) mutations) is due to the presence of an elongated alpha 2-mRNA which uses an alternate location as polyadenylation site. The relative levels zeta-mRNA varied considerably; the highest levels were found in patients with the -(alpha)20.5/-alpha or - -SEA/-alpha deletional types but not in those with the -(alpha)20.5/alphaPA-2 alpha, -(alpha)20.5/alpha-5nt alpha, or - -SEA/alphaCS alpha nondeletional types. No definitive explanation can be given for these differences; perhaps certain sequences that are part of some of the alpha-thal-1 deletions are important for the suppression of the zeta-globin gene.

Adolescent↗
PubMed1996

A novel (delta beta)(0)-thalassemia due to a approximately 30-kb deletion observed in a Turkish family.

A new deletion of the beta-globin gene cluster was characterized in a Turkish family. A 6-year-old male and his father were heterozygotes for this deletion. They presented with mild hypochromic microcytic anemia associated with elevated Hb F (15%) and normal Hb A2 levels (2.0%). This newly described Turkish type (delta beta)(0) thalassemia has a deletion of about 30 kb. The 5' breakpoint of this deletion starts approximately 1.5 kb downstream of an enhancer-like sequence of the A gamma-globin gene. The 3' endpoint is located in the L1 repeat sequence (Kpnl site) 3' to the beta-globin gene. The new deletion (Turkish type 3) is quite similar to that of the Indian (delta beta)(0)-thalassemia deletion in size and 5' breakpoint. However, the 3' endpoint in this new deletion is 2.5 kb shorter than the Indian type.

Adult↗
PubMed1996

A locus for Fanconi anemia on 16q determined by homozygosity mapping.

We report the results of a genomewide scan using homozygosity mapping to identify genes causing Fanconi anemia, a genetically heterogeneous recessive disorder. By studying 23 inbred families, we detected linkage to a locus causing Fanconi anemia near marker D16S520 (16q24.3). Although -65% of our families displayed clear linkage to D16S520, we found strong evidence (P = .0013) of genetic heterogeneity. This result independently confirms the recent mapping of the FAA gene to chromosome 16 by Pronk et al. Family ascertainment was biased against a previously identified FAC gene on chromosome 9, and no linkage was observed to this locus. Simultaneous search analysis suggested several additional chromosomal regions that could account for a small fraction of Fanconi anemia in our families, but the sample size is insufficient to provide statistical significance. We also demonstrate the strong effect of marker allele frequencies on LOD scores obtained in homozygosity mapping and discuss ways to avoid false positives arising from this effect.

Chromosome Mapping↗
PubMed1995

A new Turkish type of beta-thalassaemia major with homozygosity for two non-consecutive 7.6 kb deletions of the psi beta and beta genes and an intact delta gene.

In a 2.5-month-old infant with beta-thalassaemia major, DNA analysis of the gamma-beta region revealed homozygosity for two large deletions removing the entire psi beta and beta regions including their 5' promoter regions but leaving the delta gene intact. The downstream deletion was predicted to be 7.6 kb in length extending from a point 1.5 kb on the 3' side of the delta-globin gene to about 1.8 kb on the 3' side of the beta-globin gene. The upstream deletion, which was also about 7.6 kb, extended from a point 1.5 kb on the 5' side of the psi beta-globin gene to about 4.5 kb on the 3' of the psi beta gene. The delta-globin gene was intact. From the phenotypic expression of the disease it is concluded that removal of the psi beta gene probably prevents derepression of the gamma gene that has previously been observed in the absence of the promoter region of the beta gene and the switch mechanism from gamma to beta gene expression may take place earlier than expected.

Blotting, Southern↗
PubMed1994

Audiologic and impedancemetric findings within thalassaemic patients.

The objective of this study is to investigate hearing losses in thalassaemic patients. This study was conducted on 34 thalassemic patients of which 27 of them had thalassaemia major and the remaining 7 had thalassaemia intermedia. Six (11.11%) of the 54 ears with thalassaemia major were found to have normal hearing. Thirty-two ears (59.26%) had conductive hearing loss, 8 ears (14.81%) had mixed type of hearing loss. Moreover, in this group, there was no ear which had pure sensorineural hearing loss. Of the majority of patients having thalassaemia major and thalassaemia intermedia, an air bone gap was found even though there was no negative pressure in the middle ear. In these patients a high degree of static compliance and normal shaped, stiff amplitude, normal pressure tympanograms were observed. Moreover, in most of these patients acoustic reflexes were not obtained. These findings are rather interesting since they show the pathological changes which may cause stiffness in the middle ear sound transmission system.

Acoustic Impedance Tests↗
PubMed1994

Possible factors influencing the haemoglobin and fetal haemoglobin levels in patients with beta-thalassaemia due to a homozygosity for the IVS-I-6 (T-->C) mutation.

We have collected haematological, haemoglobin (Hb) and DNA sequence data for 29 patients with a homozygosity for the IVS-I-6 (T-->C) mutation with the intention of identifying factors contributing to the observed variability in the severity of the disease. None of the patients had received blood transfusion therapy for at least 6 months prior to the study. Hb levels varied from 5.0 to 9.9 g/dl. Patients with high Hb F (more than 1.5 g/dl or > 20%) had high total Hb levels (7.5-9.7 g/dl) but some with low Hb F also had high total Hb levels; two had a concomitant alpha-thalassaemia-2 (alpha-thal-2) heterozygosity. An inverse correlation between the Hb F and Hb A2 levels was observed. The majority of the patients were homozygous for haplotype VI (49/58 chromosomes) but haplotypes IV (2/58) and VII (7/58) were also present. The only haplotype IV homozygote had high Hb F levels with high G gamma values and the C-->T mutation at position -158 in the G gamma promoter, while both high and low Hb F levels were observed among patients with haplotypes VI and VII. Analysis of sequence variations in regulatory regions included the 5' hypersensitive sites (HS) 4. 3 and 2 of the locus control region (LCR), the G gamma and A gamma 5' flanking regions, the second intervening sequence (IVS-II), and the 5' beta-globin gene region in two patients with high Hb F (one homozygote each for haplotypes VI and IV), and in two patients with low Hb F levels (one homozygote each for haplotypes VI and VII). Haplotype specific differences were observed in the LCR 5' HS-2 and in the G gamma and A gamma flanking and IVS-II regions; however, no differences were present between the low and high Hb F-producing haplotype VI chromosomes, suggesting a major role for factors which are not linked to the beta-globin gene cluster in mediating gamma-globin gene expression in patients with this type of beta-thal.

Adolescent↗
PubMed1994

Chronic autoimmune hemolytic anemia in children: a report of four patients.

Four children, ages seven to ten years, with direct antiglobulin test (DAT)-positive chronic hemolytic anemia are presented. The patients were followed for 3 to 10 years. Autoantibody against red cell antigens was nonspecific IgG type in all of the patients. In one of the four patients, anemia was associated with splenomegaly and jaundice. In this patient, the third component of the complement was also detected on the red cell surface. In one patient, serum IgA deficiency and frequent pulmonary infections were associated with the disease. This patient developed rheumatoid arthritis five years after diagnosis of hemolytic anemia. The third patient initially had thrombocytopenia subsequently developed DAT-positive hemolytic anemia, vitiligo and alopecia without any evidence of serologic changes suggestive of collagen vascular disorders. In these three patients, partial response was obtained with steroid therapy. The fourth patient developed DAT-positive hemolytic anemia twice during the five year follow-up period. Anemia resolved completely with steroid therapy in two months during the first episode, and in five months in the second. Generalized and peripheral lymphadenopathies which developed at the time of the second hemolytic anemia episode have persisted for the last three years. Administration of cyclosporine in two of the four patients did not result in any amelioration of the symptoms.

Anemia, Hemolytic, Autoimmune↗