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Biomedical subjects

C Altay

Publications and source records attributed to C Altay.

At least 19 recordsLinked to original sources
PubMed2002

Importance of RDW value in differential diagnosis of hypochrome anemias.

Red cell distribution width (RDW) was studied in adults carrying delta-beta thalassemia traits (deltabeta-TT) who were 20-40 years of age (n = 29), beta thalassemia traits (beta-TT) with an age range of 18-60 years (n = 49), iron deficiency anemia (IDA) in individuals aged 1-18 years (n = 27), and in controls with an age range of 20-40 years (n = 20). Although red blood cell count, MCV, and MCH values showed no statistically significant differences between deltabeta-TT and beta-TT, the mean RDW value was significantly higher in deltabeta-TT (20.14 +/- 1.21) compared to beta-TT (14.88 +/- 1.77) (P < 0.001). No difference was observed between the means of RDW in deltabeta-TT and IDA (18.00 +/- 1.94) (P > 0.05). A significant rise in RDW in IDA 5-7 days after initiation of iron therapy (P = 0.00) which was continued to rise up to the 4(th) week of therapy was suggested as an important tool in differentiation of IDA from deltabeta-TT. These observations could be kept in mind in the differential diagnosis of deltabeta-TT from beta-TT and IDA by determining the red blood cell count, red cell indices, and RDW only.

Adolescent↗
PubMed2001

Evidence for the existence of the PAF acetylhydrolase mutation (Val279Phe) in non-Japanese populations: a preliminary study in Turkey, Azerbaijan, and Kyrgyzstan.

Deficiency of plasma platelet-activating factor (PAF) acetylhydrolase resulting from a missense mutation (Val279Phe) in exon 9 of the gene has been described exclusively in the Japanese population with a very high frequency. This study describes the distribution of the mutation in Turkey and two other Turkic nations, Kyrgyzstan in central Asia and Azerbaijan bordering the Caspian Sea. Among 358 unrelated healthy subjects studied from Turkish population, only 3 had the mutation in heterozygous state (0.84%). Family studies also revealed the presence of homozygous individuals in close relatives of one of these subjects. Among 143 healthy subjects studied from Kyrgyzstan, 12 were heterozygous for the mutation (8.4%). No mutation was detected among 100 healthy individuals studied from Azerbaijan. However, it was suggested that the number of subjects was not enough to draw any conclusion about the prevalence of the mutation in the populations studied. Contrary to the previous notions, identification of the mutation in Turkey and Kyrgyzstan shows the existence of the mutation in non-Japanese populations as well.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2001

beta-Thalassaemia intermedia in a Turkish girl: homozygosity for G-->A substitution at +22 relative to the beta-globin cap site.

We provide the first description of a homozygote patient for the G-->A substitution in the 5' UTR of the beta-globin gene. The proband was a 17-year-old girl with beta-thalassaemia intermedia who had never received a blood transfusion. The physical examination revealed a well-developed women with no facial or bony abnormalities. There was mild paleness and mild splenomegaly which was 2 cm below the costal margin. The haemoglobin (Hb) was 7.6 g/dl, Hb A(2) 5.4% and Hb F 14.6% of the total Hb. The Hb A(2) of both parents was 3.5%. The Hb F level in the mother and father were 0.9, 1.2% and the mean cell volume (MCV) value was 70 and 72 fl respectively. DNA analysis of the beta-gene region of the propositus revealed homozygosity for a G-->A substitution at nucleotide +22 relative to the beta-gene cap site, within a functional downstream region that was referred to as the DCE (downstream core element). In addition to the data obtained previously from in vitro transcription assays, clinical findings and in vivo expression studies gave some valuable clues about the effect of +22 G-->A mutation on the expression of beta-gene. Phenotypic expression of this homozygous patient is highly suggestive that G-->A substitution at nt +22 confers a relatively mild (silent) beta(+)-thalassaemia phenotype.

5' Untranslated Regions↗
PubMed2001

Homozygosity for Hb E-Saskatoon [beta22(B4)Glu-->Lys] in a Turkish patient.

A 30-year-old female who is homozygous for a Hb E-like abnormal hemoglobin and her immediate relatives were studied. Clinical examination of the proband revealed no abnormality. Routine hematological analysis showed that her hemoglobin level was 12 g/dL, MCV 82 fL, MCH 28 pg, RDW 15%. DNA sequence analysis indicated the presence of a G-->A substitution at codon 22 corresponding to an abnormal hemoglobin, namely Hb E-Saskatoon [beta22(B4)Glu-->Lys (GAA-->AAA)]. Absence of any abnormalities in clinical and routine hematological investigations of the homozygous patient indicated that the phenotypical expression of the Hb E-Saskatoon is very mild. Using a reverse transcription-polymerase chain reaction technique, the alpha/beta and betaX/betaA-mRNA (X = Hb E-Saskatoon) ratios were determined. Normal alpha/beta and betaX/betaA-mRNA ratios were found in the homozygous patient and in all heterozygotes, indicating that the respective mutation did not alter the stability of the mRNA. FokI restriction enzyme analysis of the polymerase chain reaction products obtained from the genomic DNA and/or beta-globin mRNA made it possible for rapid diagnosis of Hb E-Saskatoon, and for its differentiation from Hb E [beta26(B8)Glu-->Lys (GAG-->AAG)]. Analysis of the restriction fragment length polymorphism (RFLP) in the beta-globin gene complex of the index patient and of another unrelated family with a compound heterozygosity for Hb E-Saskatoon and beta-thalassemia revealed that the Hb E-Saskatoon mutation shared a common allele.

Adult↗
PubMed2000

Association of complementation group and mutation type with clinical outcome in fanconi anemia. European Fanconi Anemia Research Group.

Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder. Clinical care is complicated by variable age at onset and severity of hematologic symptoms. Recent advances in the molecular biology of FA have allowed us to investigate the relationship between FA genotype and the nature and severity of the clinical phenotype. Two hundred forty-five patients from all 7 known complementation groups (FA-A to FA-G) were studied. Mutations were detected in one of the cloned FANC genes in 169 patients; in the remainder the complementation group was assigned by cell fusion or Western blotting. A range of qualitative and quantitative clinical parameters was compared for each complementation group and for different classes of mutation. Significant phenotypic differences were found. FA-G patients had more severe cytopenia and a higher incidence of leukemia. Somatic abnormalities were less prevalent in FA-C, but more common in the rare groups FA-D, FA-E, and FA-F. In FA-A, patients homozygous for null mutations had an earlier onset of anemia and a higher incidence of leukemia than those with mutations producing an altered protein. In FA-C, there was a later age of onset of aplastic anemia and fewer somatic abnormalities in patients with the 322delG mutation, but there were more somatic abnormalities in patients with IVS4 + 4A --> T. This study indicates that FA patients with mutations in the FANCG gene and patients homozygous for null mutations in FANCA are high-risk groups with a poor hematologic outcome and should be considered as candidates both for frequent monitoring and early therapeutic intervention. (Blood. 2000;96:4064-4070)

Abnormalities, Multiple↗
PubMed2000

Spectrum of mutations in the Fanconi anaemia group G gene, FANCG/XRCC9.

FANCG was the third Faconi anaemia gene identified and proved to be identical to the previously cloned XRCC9 gene. We present the pathogenic mutations and sequence variants we have so far identified in a panel of FA-G patients. Mutation screening was performed by PCR, single strand conformational polymorphism analysis and protein truncation tests. Altogether 18 mutations have been determined in 20 families - 97% of all expected mutant alleles. All mutation types have been found, with the exception of large deletions, the large majority is predicted to lead to shortened proteins. One stop codon mutation, E105X, has been found in several German patients and this founder mutation accounts for 44% of the mutant FANCG alleles in German FA-G patients. Comparison of clinical phenotypes shows that patients homozygous for this mutation have an earlier onset of the haematological disorder than most other FA-G patients. The mouse Fancg sequence was established in order to evaluate missense mutations. A putative missense mutation, L71P, in a possible leucine zipper motif may affect FANCG binding of FANCA and seems to be associated with a milder clinical phenotype.

Amino Acid Sequence↗
PubMed2000

Molecular analysis of turkish beta-thalassemia heterozygotes with normal Hb A2 levels.

Four parents of three unrelated families who are obligatory beta-thalassemia heterozygotes and two parents with Hb Knossos are presented. In these subjects, although the red blood cell counts and red cell indices were compatible with beta-thalassemia trait, the Hb A2 values were between 1.9-2.9% of the total hemoglobin. Examination of the delta-globin gene by Southern blot, restriction endonuclease analysis, and by direct sequencing of amplified DNA revealed the presence of the (delta0) -7.2 kb Corfu type deletion, the (delta+) codon 27 (G-->T) and (delta0) IVS-I-2 (T-->C) mutations in trans or in cis with a severe beta-thalassemia allele, and the (delta0) codon 59 (-A) deletion in cis with the betaKnossos allele.

Adult↗
PubMed2000

Beta-thalassemia intermedia associated with homozygosity for the -87 (C-->T) mutation in a Turkish family.

We report on two siblings with beta+-thalassemia intermedia. Molecular studies of the beta-globin gene indicated that the patients are homozygous for the -87 (C-->T) mutation. This genotype has not been previously described. Homozygosity for the -87 (C-->T) mutation produces a mild form of beta+-thalassemia associated with moderate Hb F elevation (26-38%) and highly elevated Hb A2 (10-8.6%) levels, respectively. Hematological parameters of homozygous -87 (C-->G) and -87 (C-->A) mutations, and compound heterozygous patients with either C-->T, C-->G, or C-->A at -87 and one of the severe beta+- or beta0-thalassemia mutations, are given for comparison.

Adult↗
PubMed1999

Myelodysplastic syndrome (MDS) associated with increased hemoglobin F and trisomy 8: presentation of a patient.

A 7.5 year old boy with myelodysplastic syndrome (MDS) of CMML type associated with trisomy 8 and elevated hemoglobin F (Hb F) value is presented. Hematological evaluation of the patient revealed that the Hb was 10 g/dl, MCV 110 FL, platelets 58 X 10(9)/l, WBC 5.4 X 10(9)/l with 24% atypical monocytes. Karyotype analysis revealed 47, XY, +8. Hb F value was 21% which was distributed heterogeneously among red cells. PCR amplified cDNA copies of circulating reticulocyte mRNA were used to measure the relative amounts of alpha-, beta-, and gamma- globin. There was marked increases in both alpha/beta mRNA ratio (20%) and gamma/(gamma+beta) mRNA ratio (35%) in the patient compared to normal subjects. The study indicated that increased transcription of alpha and gamma genes are partly responsible for the elevation of Hb F in MDS.

Base Sequence↗
PubMed1999

Beta thalassaemia: a report of 20 children.

Beta-thalassaemias have a wide variety of musculoskeletal system manifestations. In this cross-sectional study, we aimed to investigate the frequency and features of musculoskeletal system problems in children with beta-thalassaemia. A total of 20 beta thalassaemic patients with an average age of 13.8 years were enrolled in the study. In all patients studied, detailed history regarding musculoskeletal involvement was taken and locomotor examinations were performed. All patients underwent radiographic examination with standing anteroposterior and lateral X-rays of the spine. Two physicians blinded for the diagnosis used Cobb technique for determining the degree of scoliosis. In 12 of 20 patients (60%) locomotor system involvement was found. Most frequent complaints were arthralgia and low back pain in 30% and 25% of patients respectively. Scoliosis was detected radiologically in 40% of patients with a lateral curve of at least 5 degrees Cobb.

Adolescent↗
PubMed1999

Heterogeneous spectrum of mutations in the Fanconi anaemia group A gene.

Fanconi anaemia (FA) is a genetically heterogeneous autosomal recessive disorder associated with chromosomal fragility, bone-marrow failure, congenital abnormalities and cancer. The gene for complementation group A (FAA), which accounts for 60-65% of all cases, has been cloned, and is composed of an open reading frame of 4.3 kb, which is distributed among 43 exons. We have investigated the molecular pathology of FA by screening the FAA gene for mutations in a panel of 90 patients identified by the European FA research group, EUFAR. A highly heterogeneous spectrum of mutations was identified, with 31 different mutations being detected in 34 patients. The mutations were scattered throughout the gene, and most are likely to result in the absence of the FAA protein. A surprisingly high frequency of intragenic deletions was detected, which removed between 1 and 30 exons from the gene. Most microdeletions and insertions occurred at homopolymeric tracts or direct repeats within the coding sequence. These features have not been observed in the other FA gene which has been cloned to date (FAC) and may be indicative of a higher mutation rate in FAA. This would explain why FA group A is much more common than the other complementation groups. The heterogeneity of the mutation spectrum and the frequency of intragenic deletions present a considerable challenge for the molecular diagnosis of FA. A scan of the entire coding sequence of the FAA gene may be required to detect the causative mutations, and scanning protocols will have to include methods which will detect the deletions in compound heterozygotes.

Base Sequence↗
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↗