[Show abstract][Hide abstract]ABSTRACT: 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 α-thalassemia-2 heterozygotes among Black babies with less than 1% Hb Bart's at birth and a high incidence of α-thalassemia-2 among Sardinians, but not among Sicilian, Turkish, and Spanish babies. A relatively high incidence of ζ-thalassemia was present among Black babies only, while triplicated ζ was seen in four of the five populations. Two Black babies were each found to have a different θl deletion; two Sardinian babies had a newly discovered β 2.5 kb deletion between ζ and ψζ; four babies had the rare Bgl II polymorphism between ψζ and ψα; and one Black baby lacked the Eco RI site 3’ to ζ Quantitation of the ζ chain by reversed phase high performance liquid chromatography showed that two-thirds of the babies with four α genes (αα/αα) had levels between 0.1 and 1.0%, while nearly 90% of the babies with -α/αα had similar levels (averaging 0.2% for αα/αα 0.35% for -α/αα 0.75% for -α/-α). Additional data indicated that the occurrence and level of ζ are related to the level of β, i.e. the gestational age. The presence of a ζ triplication did not affect the level of ζ in cord blood. The extensive search for γ-globin gene anomalies resulted in the discovery of a chromosome with five γ genes, γ-Thalassemia was rare in all populations, while the -Gγ-Gγ- gene arrangement was mainly observed among Black babies; this arrangement is primarily responsible for high Gγ 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 Gγ was confirmed for adult blood samples. A search for possible anomalies in the -δ-β- region through gene mapping with Eco RV gave negative results except for the discovery of a polymorphic site 5’ to δ in one of the 371 Black babies tested.
[Show abstract][Hide abstract]ABSTRACT: We recently examined a 16-year-old high school student who participated in a survey for Hemoglobinopathies in an Anatolian city in Turkey. Analysis if his hemoglobin (Hb) showed the presence of an electrophoretically slow-moving variant (at pH 8.6, about as Hb S) which, upon further examination, was also seen in his father, one brother, and one sister.
[Show abstract][Hide abstract]ABSTRACT: The testing program of cord blood samples for hemoglobin (Hb) abnormalities, presently conducted in a few centers of Turkish Universities, sometimes detects rare variants which may or may not affect the health of the newborn. One example to be described here is O-Padova which has been observed once before (1). The variant was detected in the blood of a newborn girl by starch gel electrophoresis at pH 9.0 (2); the mobility of the variant (presumably α2Xγ) was slightly slower than that of Hb C (or α2β26 Glu→Lys) (Fig. 1). Red cell lysates from the father and a 2-year-old brother contained a different Hb component with a mobility distinctly faster than that of Hb A2 or of Hb C; a minute quantity of a similar component (presumably α2X2) was also present in the cord blood red cell lysate of Baby E (Fig. 1). The baby was retested when 40 days old; her hematological values and those of her father and brother were normal (Table I). Quantitation by cation exchange high performance liquid chromatography (HPLC) (3) gave total Hb X values of 15.4% for the baby (Hb X + Hb Fx), 18.3% for the father (Hb X + Hb X2), and 12.8% for the brother (Hb X + Hb X2) (see also Table I).
[Show abstract][Hide abstract]ABSTRACT: Two homozygous δ0 β0-thalassemia patients, one with the GγAγ type and the other with the Gγ type, and their heterozygous parents are described. Red cell indices among the heterozygotes with the GγAγ type of δ0β0-thalassemia were markedly different from those in heterozygotes with the Gγ type. However, the imbalance in in vitro hemoglobin synthesis was quite similar in the two heterozygous conditions. The same was observed for the homozygous patients; the in vitro chain synthesis was severely imbalanced as seen in β-thalassemia major. The clinical and some of the hematological findings were milder in the Gγ-δ0 β0-thalassemia homozygote than in the GγAγ - δ0 β0-thalassemia homozygote. The death of a sibling of the Gγ - δ0 β0-thalassemia homozygote with a diagnosis of thalassemia major suggests that both types of δ0 β0 -thalassemia could follow a severe clinical and hematological course. The discovery of the Gγ type of δ0 β0-thalassemia in a Turkish child shows that two types of δ0 β0 - thalassemia can be found in that country. Differentiation between the two types can only be made through structural analyses of Hb F.
[Show abstract][Hide abstract]ABSTRACT: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common erythrocyte enzyme deficiency in the world. The epidemiological, biochemical and molecular studies on G6PD enzyme deficiency performed over the past 50 years are summarized herein, with special emphasis on the findings of studies related to the enzyme deficiency in Turkey.
[Show abstract][Hide abstract]ABSTRACT: To investigate the morphology and function of platelets in nephropathic cystinosis (NC).
Seven patients (mean age, 6.5 years; SD, 20 months) with NC were investigated. Their platelets were examined by transmission electron microscopy (TEM) and the characteristics of the dense granules (DGs) were determined by mepacrine labelling and the uranaffin reaction. Bleeding time, turbidometric aggregation, and luminescence aggregation were studied and intraplatelet cystine was measured.
Increased intraplatelet cystine, primary and secondary aggregation defects, and the absence of ATP release were demonstrated. TEM revealed DGs of various shapes and sizes and lamellary or amorphous cytoplasmic inclusions. Viscous material had been released into the vacuolar spaces and enlarged open canalicular system. Mepacrine labelling revealed that the numbers of DGs/platelet were comparable between the patients and the controls (mean, 2.9 (SD, 0.22) v 3.32 (0.18); p = 0.34). The uranaffin reaction revealed that the numbers of type 1, 3, and 4 DGs were comparable between the patients and the controls, but that there were fewer type 2 DGs in the patients (mean, 8.5 (SD, 1.95) v 17.22 (1.58); p = 0.01). TEM for platelet aggregation revealed a lack of induction and/or defective execution and/or delayed transmission. The patients' intraplatelet cystine concentrations were higher than the controls (mean, 1.56 (SD, 0.84) v 0.08 (0.01) nmol/mg protein; p = 0.009).
This is the first report to demonstrate raised intraplatelet cystine, abnormal platelet ultrastructural findings, and defective aggregation in NC.
Full-text available · Article · Oct 2005 · Journal of Clinical Pathology
[Show abstract][Hide abstract]ABSTRACT: A boy presented at age 4 years with severe congenital hemolytic anemia characterized by highly elevated reticulocyte count (30-50%) and prominent basophilic stippling. Hb had been 4 g/dL at age 7 months. The patient was on a monthly transfusion regimen up to the age of 7 years, when he underwent splenectomy. After removal of the spleen, his Hb stabilized at 11 g/dL. No abnormal pattern was detected in hemoglobin electrophoresis at pH 9 and 6. In-vitro globin synthesis revealed the presence of an abnormal beta-chain in front of the gamma-chain. The beta(A)/beta(X) ratio was 0.77 at 30 min and 0.74 at 2 hr of incubation. Molecular analysis revealed that the patient had GCC-->GAC alteration at codon 27 (beta27(B9)Ala-->Asp) causing the abnormal hemoglobin Volga. The beta-cDNA derived from the beta-Hb Volga allele could be differentiated from HbA beta-cDNA on silver-stained gel. No imbalance in the mRNA of beta(A)/beta(Hb Volga) ratio was observed.
Article · Aug 2004 · American Journal of Hematology
[Show abstract][Hide abstract]ABSTRACT: Fanconi anemia (FA) is an autosomal recessive disorder characterized by multiple congenital abnormalities, bone marrow failure, cancer susceptibility and cellular sensitivity to cross-linking agents. To date, at least eight complementation groups (A-C, D1, D2, E-G) have been described and seven FA genes have been cloned. The protein products of these genes interact in a common pathway in response to DNA damage with cross-linking agents or during the S-phase of cell cycle. Five FA proteins (A, C, E, F, G) form a nuclear complex and mediate activation of D2 protein (FANCD2) by monoubiquitination. Activated FANCD2 is targeted to a nuclear DNA repair foci where it interacts with the breast cancer susceptibility (BRCA1, BRCA2) and other DNA repair proteins. Recent studies have revealed that FANCD1 and BRCA2 are in fact the same gene. On the other hand, the ataxia telangiectasia kinase (ATM) phosphorylates FANCD2 protein in response to ionizing radiation. Phosphorylated FANCD2 activates S-phase checkpoint to arrest cell cycle progression and allow time for DNA repair. These findings have indicated that FANCD2 functions at the intersection of two independent signaling pathways of the DNA repair.
Article · Jan 2003 · Cocuk Sagligi ve Hastaliklari Dergisi
[Show abstract][Hide abstract]ABSTRACT: 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.
Article · Feb 2002 · American Journal of Hematology
[Show abstract][Hide abstract]ABSTRACT: The case of an 8-year-old male child with severe kernicterus sequelae is presented in this paper. The child's hemoglobin value varied between 6.0 and 10.8 g/dL and his reticulocyte count ranged between 3.4 and 46.0% during the steady-state condition and hyperhemolytic crisis, respectively. A chronic hemolytic type of red cell G6PD deficiency was diagnosed. DNA studies indicate that the mutation was G6PD Guadalajara 1159 C --> T (387 Arg --> Cys) that is situated at the NADP binding site. Additionally, extra nucleotides of (TA) in the A(TA)n TAA motif of the promoter region of the uridine diphosphate-glucuronosyltransferase gene (UGT-1 A) were found to be homozygous in the patient. The coexistence of Gilbert syndrome with a chronic type of G6PD deficiency was suggested as a cause of neonatal hyperbilirubinemia leading to kernicterus.
Article · Jan 2002 · Pediatric Hematology and Oncology