The Spectrum of β-Thalassemia Mutations in Siirt Province,Southeastern Turkey

Abstract

β-Thalassemia (β-thal) is the most common hereditary genetic blood disorder. The aims of this study were: (i) to determine the mutation types and the frequency of these mutations in β-thal patients to obtain the ethnic origins of the population in Siirt Province; (ii) to evaluate the pathogenicity of these mutations by performing in silico analysis; (iii) to reveal the genotype-phenotype correlation by comparing the clinical manifestation of our patients to the specific mutations in this population. This study included 34 patients (18 males and 16 females) with a mean age of 9.1?±?3.6 years (range 3–16 years). All mutations were determined using sequence analysis methods, and the mutations were analyzed using bioinformatics tools. Thirteen different mutations were detected in the patients: IVI-I-110 (G>A) (HBB: c.93-21G>A) (38.9%); IVS-II-1 (G>A) (HBB: c.315_1G>A) (11.1%); –30 (T>A) (HBB: c.-80T>A) (9.25%) and IVS-I-1 (G>A) (HBB: c.92?+?1G>A) (9.25%), were the most common, and these mutations constituted 68.5% of the cases. Missense codon 6 (A>T) (HBB: c.20A>T) was not pathogenic; however, all the intronic mutations (IVS-I-1, IVS-I-110, IVS-II-1) and frameshift mutations [codon 44 (–C) (HBB: c.135delC) and codons 36/37 (–T) (HBB: c.112delT)] resulted in disease. These mutations can be used to determine the ethnic origin of the Siirt population and, in affected pregnant women, to develop prenatal strategies. A fatal phenotype can be identified by in silico analysis; however, mutations that are unknown prior to marriage, pregnancy, and childbirth or new mutations can be less accurately identified.     

Association of Hb Q-Thailand with Heterozygous Hb E in a Chinese Patient

We describe a Chinese patient who was heterozygous for both Hb Q-Thailand [α74(EF3)Asp→His] and Hb E [β26(B7)Gly→Asp, GAG→GTG]. Interaction of the α^Q-Thailand and β^E chains leads to a hemoglobin (Hb) variant, namely Hb QE, which differs in electrophoretic mobility and high performance liquid chromatography (HPLC) profiles and in the amount of the Hb Q-Thailand variant present in the blood.     

Unstable and Thalassemic α Chain Hemoglobin Variants: A Cause of Hb H Disease and Thalassemia Intermedia

We report an update of the α-globin gene point mutations resulting in structural modification associated with an α-thalassemia (α-thal) phenotype. These variants, barely symptomatic in the heterozygous state, are either unstable due to folding defects and/or defects in binding to α-hemoglobin stabilizing protein (AHSP). This is predicted to result in precipitation of the unstable α chains or Hb variant, a concomitant decrease in the overall quantity of normal α-globin in the red cells and a potential degree of anemia and possibly, hemolysis. Genotype/phenotype correlation and potential genetic risk in combination with common or less common α-thal defects are discussed.     

A Rare Thalassemic Syndrome Caused by Interaction of Hb Adana [α59(E8)Gly→Asp] with an α+-Thalassemia Deletion: Clinical Aspects in Two Cases

Hb Adana is a highly unstable and rare α-globin hemoglobin (Hb) variant, to date described in only three families, in interaction with other α-thalassemia (α-thal) deletions. We describe the clinical and hematological findings in two cases from independent families of Albanian origin, who have an interaction of the codon 59 (Gly→Asp) α2-globin gene variant in trans to a 3.7 kb α⁺-thal deletion (α^{codon 59}α/?α). We report their presenting symptoms and laboratory findings as well as complications and differences in their clinical management. Both cases can be characterized as thalassemia intermedia and illustrate the problems associated with selecting the most appropriate options for patient management, especially in cases with rare underlying genotypes.     

补肾生血颗粒对慢性肾衰实验性大鼠血TNF和EPO的作用

[目的]探讨补肾生血颗粒对慢性肾功能衰竭大鼠改善肾性贫血作用及血EPO、TNF的影响。[方法]采用腺嘌呤建立大鼠贫血模型,随机分为模型对照组、中药治疗组(补肾生血颗粒)、西药治疗组(促红素EPO)、中西药联合治疗组(补肾生血颗粒、EPO联用)。测血RBC、Hb、HCT、肾功、EPO及肿瘤坏死因子(TNF)的指标。[结果]与中药组及中西药联合应用组相比,补肾生血颗粒治疗肾性贫血的效果与EPO无明显差异(P>0.05),稍逊于中西药联合应用组(P<0.05),并能明显降低血BUN、Cr的含量(P<0.01),减轻肾组织病理损害,还可降低血TNF,提高血EPO的水平。[结论]补肾生血颗粒能有效治疗肾性贫血并能明显改善肾功能,提高血EPO含量,还有降低血TNF的作用。     

工业区环境铅对儿童血红蛋白及智商的影响

目的 :以锌卟啉 (zpp)作为铅生物学标志物 ,探讨铅对儿童血红蛋白及智商的影响。方法 :对 35 5名工业区正常儿童进行zpp流行病学调查 ,测定血红蛋白 (Hb)、智商 (IQ)并进行分层分析和逐步回归分析。结果 :在用zpp0 .6 8μmol/L分层后 ,zpp >0 .6 8μmol/L组儿童Hb、IQ明显低于zpp <0 .6 8μmol/L组儿童 ,尽管这些指标仍然在正常范围 ,但已存在明显统计学差异。结论 :用zpp作为生物学效应指标筛选儿童铅中毒有一定实用价值。以生物效应的结果判定 ,zpp正常值界临水平应为 0 .6 8μmol/L。     

Hemoglobin sickle-lepore: Report of two siblings and review of the literature

Hemoglobin Lepore is composed of two normal α-globin chains and two δ-β fusion globin chains that result from nonhomologous crossing over of genetic material during meiosis. The doubly heterozygous condition of sickle hemoglobin with Lepore hemoglobin (Hb S-Lepore) is rare, having been described previously in only nine patients. We report two siblings with Hb S-Lepore who have similar hematologic characteristics but a marked difference in clinical severity. © 1993 Wiley-Liss, Inc.     

399例健康育龄妇女正常二胎自然分娩后3个月内检验血Hb分析

我站检验科对女性血Hb值是否满足输卵管结扎的手术要求,进行了为我站施行输卵管结扎手术的血Hb检验分析。结果表明:健康育龄妇女二胎正常分娩后3个月内行女性输卵管结扎术,除个别检验血Hb低于9.5g为贫血者暂不宜施术外,绝大多数血Hb正常,不影响施术。因此,健康育龄妇女二胎正常分娩后3个月内可以行输卵管结扎术。现报告如下。     

Postnatal changes in the quantities of globin chains and hemoglobin types in two babies with Hb H disease

We have studied two babies with Hb H disease from birth to about six months of age and analyzed the changes in the relative quantities of the five globin chains (α, β, ^Gγ, ^Aγ) and the four hemoglobins (Hb F, Hb A, Hb Bart's, Hb H) using different high performance liquid chromatography procedures. The types of Hb H disease were —(SEA)/-α (3.7 kb) and —(Fil)/-α (3.7 kb); the larger—(Fil) deletion includes the functional 2-globin gene, explaining the higher chain level in the baby with the —(SEA)/-α (3.7 kb) type. The functional hemoglobin level at birth (Hb A + Hb F) was 11 to 12 g/dl with 3 to 4 g/dl Hb Bart's (γ4). Only 5% of the “fast-moving” hemoglobin was Hb H (β₄). The level of Hb F at birth was low (less than 50% of the total Hb A + Hb F). After birth, the α and γ chain production decreases rapidly resulting in a severe anemia (total functional hemoglobin ～7 g/dl) at 30 to 60 days postnatally, improving gradually to 8.5–9.5 g/dl at age of three months. The preferential formation of Hb A over Hb F at birth, and presumably prenatally, has the advantage that the level of the highly unstable Hb H is kept low; it also results in low levels of Hb F impairing the oxygen transfer capability of the fetal blood. © 1993 Wiley-Liss, Inc.