我国异常血红蛋白研究─9例Hb New York β 113（G15）Val－Glu的一级结构分析

本文报道了９例Ｈｂ　Ｎｅｗ　Ｙｏｒｋ　β１１３（Ｇ１５）Ｖａｌ－Ｇｌｕ的异常血红蛋白，这在国内的贵州、福建、特别是在北方的河南尚无报道，并且在侗族中尚属首次报道。     

Report on Ten Years’ Experience of Premarital Hemoglobinopathy Screening at a Center in Antalya,Southern Turkey

Thalassemia and hemoglobinopathies are a major public health problem in Turkey. Hemoglobinopathy prevention programs (HPPs) were started in 33 provinces situated in Thrace, Marmara, Aegean, Mediterranean and South Eastern regions of Turkey in 2003. A premarital hemoglobinopathy test is mandatory and free of charge in this program. According to the Ministry of Health reports, 46 first level hemoglobinopathy diagnostic centers were established for premarital tests. Within the last 10 years, approximately 79.0% of married individuals per year were screened by the centers. While the percentage of premarital screening tests was 30.0% of all couples in 2003, it reached 86.0% in 2013. The number of newborn with thalassemia and hemoglobinopathies were 272 in 2002 and dropped to 25 in 2013. There has been a 90.0% reduction in affected births. Our hemoglobinopathy diagnostic center was established in 2003 and licensed by the Ministry of Health in 2004. We studied a total of 89,981 blood samples from premarital tests for 10 years and the incidence of β- and α-thalassemia (β- and α-thal) trait was found to be 6.57 and 3.56%, respectively. The distribution of the most common abnormal hemoglobins (Hbs) was: Hb S (HBB: c.20A?>?T) (0.31%), Hb D-Los Angeles (HBB: c.364G?>?C) (0.15%), Hb G-Coushatta (HBB: c.68A?>?C) (0.06%) and Hb E (HBB: c.79G?>?A) (0.02%). A total of 60 couples, both carrying β-thal trait, were directed to the prenatal diagnosis (PND) center in 10 years. The premarital hemoglobinopathy screening program is running successfully at our center and other centers in Turkey.     

Severe Drug-Induced Hemolysis in a Patient with Compound Heterozygosity for Hb Peterborough (HBB: c.334G>T) and Hb Lepore-Boston-Washington (NG_000007.3: g.63632_71046del)

Unstable hemoglobins (Hbs) are often overlooked in the differential diagnoses of drug-induced hemolysis. Hb Peterborough [β111(G13)Val→Phe; HBB: c.334G>T] is a rare unstable Hb variant, predominantly found in individuals of Italian descent, due to a structural defect involving a single amino acid substitution (phenylalanine for valine at position 111 of the β-globin chain). Unstable Hb variants are often inherited in the heterozygous state with Hb A (α2β2) and rarely in compound heterozygosity with other Hb variants. The presence of another variant Hb often alters the phenotype, occasionally resulting in more severe disease. Using a combination of molecular techniques; multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing, we identified a compound heterozygosity for Hb Peterborough and Hb Lepore-Boston-Washington (Hb LBW) [δ87, β116; NG_000007.3: g.63632_71046del] in a middle-aged gentleman with a history of chronic microcytic anemia and splenomegaly, presenting with severe drug-induced hemolysis, which was managed conservatively. The clinical history and presentation reflect the dual pathology due to the presence of two variant Hbs and their associated phenotypes. In this article, we discuss the phenotype resulting from the interaction of Hb Peterborough and Hb LBW and emphasize the importance of molecular testing in the diagnosis of rare Hb variants.     

Hematological Characterizations and Molecular Diagnostic Aspects of Hb Wiangpapao [α44(CE2)Pro→Ser (α1), CCG>TCG; HBA1: c.133C>T], a New α-Globin Variant Found in a Pregnant Thai Woman

We report the hematological parameters and provide a rapid molecular analysis method for detection of Hb Wiangpapao [α44(CE2)Pro→Ser, CCG>TCG; HBA1: c.133C>T], a new α-globin variant found in a pregnant Thai woman. Her red cell indices were measured by an automated blood counter. The results were: red blood cell (RBC) count 4.03?×?10¹²/L, Hb 13.1 (g/dL), packed cell volume (PCV) 0.39?L/L, mean corpuscular volume (MCV) 97.0 fL, mean corpuscular hemoglobin (Hb) (MCH) 32.5?pg, mean corpuscular Hb concentration (MCHC) 33.4?g/dL, and RBC distribution width (RDW) 9.4%. The Hb typing by high performance liquid chromatography (HPLC) showed 13.6% abnormal Hb at a retention time of 2.20?min. that was difficult to distinguish from Hb A. On the capillary electrophoresis (CE) electropherogram, this hemoglobinopathy peak did not separate from the Hb A peak. DNA sequencing showed a C>T transition at the first position of codon 44 (CCG>TCG) of the α1-globin gene that led to a substitution of proline for serine. This mutation has not been recorded in the public databases. Therefore, we named it Hb Wiangpapao as it was first discovered in the Wiangpapao District, Chiang Rai, Thailand. The multiplex allele-specific polymerase chain reaction (ASPCR) for detection of Hb Wiangpapao was developed and revealed a 510?bp specifically amplified fragment. The better understanding of hematological characterizations and the newly developed multiplex ASPCR for diagnosis of Hb Wiangpapao are useful for genetic counseling and family education.     

Case Report: Prenatal Diagnosis of Hb Hammersmith [β42(CD1)Phe→Ser; HBB: c.128T > C] in a Family with an Adult Male Patient

Hb Hammersmith [β42(CD1)Phe?→?Ser; HBB: c.128T?>?C] is a rare, unstable hemoglobin (Hb) variant. In this case report, we describe another male case of Hb Hammersmith. A 39-year-old male had hemolytic anemia, cyanosis and splenomegaly since 6 months after birth. He passed the disease allele to his daughter, a 3-year-old girl, who also had hemolytic anemia and splenomegaly. This mutation was not identified in the parents and two brothers of the father. Early prenatal diagnosis was performed in the second pregnancy in this family. This is the first case of Hb Hammersmith in an adult male patient.     

HPLC in Characterization of Hemoglobin Profile in Thalassemia Syndromes and Hemoglobinopathies: A Clinicohematological Correlation

High-performance liquid chromatography (HPLC) is a technique introduced for the accurate diagnosis of hemoglobinopathies and thalassemias. The advantage of the HPLC system is the excellent resolution, reproducibility & quantification of several normal & abnormal hemoglobin resulting in accurate diagnosis of thalassemia syndromes. The purpose of this study is to evaluate the HPLC technique in diagnosis of thalassemia syndromes and also correlate it with clinicohematological profile in these cases. A total of 110 cases were diagnosed as thalassemias and hemoglobinopathies by Bio- Rad variant II HPLC system by β-thal short program. The retention times, proportion of the haemoglobin (%), and peak characteristics for all hemoglobin (Hb) fractions were recorded. Alkaline Hb electrophoresis was performed in each case. Other tests performed were HbF estimation by Betke’s method, brilliant cresyl blue preparation for HbH inclusion bodies, sickling tests using 2 % metabisulphite and serum Ferritin estimation. Family studies were carried out wherever necessary. Of 110 cases included in the study, 87 cases were of thalassemic disorders and 23 cases were of hemoglobinopathies. Four Hb variants were identified including HbD, HbE, HbS, HbJ Oxford. There was a significant decrease in the level of HbA2 associated with iron deficiency anemia. The mean HbA2 levels in both iron deplete and iron replete groups were clearly >4 %, suggesting that HPLC identified nearly all high HbA2 β-thalassemia trait even in spite of iron deficiency.     

Inherited Hemoglobin Disorders in Guinea-Bissau,West Africa: A Population Study

The determination of the prevalence of inherited hemoglobin (Hb) disorders in endemic areas is important in order to develop programs for their control and management. The aim of this study is to determine the prevalence of inherited Hb diseases in Guinea-Bissau which is situated on the west coast of Africa, between Senegal and Guinea. One thousand and fifty-seven blood samples were collected and analyzed with high performance liquid chromatography (HPLC) for detection of β-thalassemia (thal) and Hb variants, and by gap polymerase chain reaction (gap-PCR) for the detection of deletions in the α-globin genes. We found 4.7% children were heterozygous for Hb S [β6(A3)Glu→Val, GAG →GTG], 0.2% were homozygous for Hb S, and 0.3% were heterozygous for Hb C [β6(A3)Glu→Lys, GAG →AAG]. One child had heterozygous β⁺-thal, 13.8% were heterozygous for the ?α^3.7 deletion, 1.5% were homozygous for the ?α^3.7 deletion, and 1.5% were heterozygous for the ?α^4.2 deletion. We recommend national screening programs to focus primarily on sickle cell disease, since β-thal is rare, and the observed α-thal deletions are of minor genetic importance.