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Prenatal diagnosis of severe α-thalassemia (α-thal) diseases is usually performed by DNA analysis. To establish a simple and rapid method, we evaluated the reliability of cord blood hemoglobin (Hb) analysis using an automated capillary electrophoresis (CE) system. Our results demonstrated that analysis of fetal Hb using the Sebia CapillaryS 2 is an effective, accurate and simple alternative for prenatal diagnosis of Hb Bart's (γ4) disease. [ABSTRACT FROM AUTHOR]

Hb Zurich-Albisrieden [HBA2: c.178G > C; α59(E8)Gly→Arg (α2)] is a rare nondeletional α-thalassemia (α-thal) that results from a nucleotide substitution at codon 59 of the α2-globin gene. In this report, we present a fetus with cardiomegaly, enlarged placenta and increased middle cerebral artery-peak systolic velocity (MCA-PSV) at 25 weeks’ gestation. Fetal blood sampling revealed the severe anemia [hemoglobin (Hb) level being 5.5 g/dL] and Hb H (β4) disease-like hematological findings with Hb Bart’s (γ4) level of 30.7%. Molecular analysis of the family found that the father was an Hb Zurich-Albisrieden carrier, the mother heterozygous for the – –SEAα0-thal deletion, and the fetus was a compound heterozygote for Hb Zurich-Albisrieden and the – –SEAα0-thal deletion. Therefore, this was a rare case of Hb Bart’s hydrops fetalis associated with Hb Zurich Albisrieden. [ABSTRACT FROM AUTHOR]

Nondeletional α-thalassemia (α-thal) is the result of point mutations in critical regions of the α-globin genes, affecting mRNA processing, mRNA translation, or α-globin stability. Hb Constant Spring (Hb CS,HBA2: c.427T > C) is the most common nondeletional α-thal that results from a nucleotide substitution at the termination codon of the α2-globin gene. Hb Quong Sze (Hb QS, HBA2: c.377T > C) is another nondeletional α-thal in South China with the missense mutation at codon 125 of the α2-globin gene making this hemoglobin (Hb) variant highly unstable. Although homozygosity for Hb CS (αCSα/αCSα) or Hb QS (αQSα/αQSα) has been reported, clinical pictures vary from severe hemolysis that developed early in life to only mild anemia, no clinical phenotypic data of compound heterozygosity for Hb CS/Hb QS (αCSα/αQSα) has been described. In this report we describe an adult case with such a compound heterozygosity who presented with a mild α-thal. [ABSTRACT FROM AUTHOR]

Tyr35β is located at the convergence of the α1β1, α1β2 and α1α2 interfaces of Hb A. We here report a Chinese family in whom the codon 35 (A > G) (HBB: c.107A > G) mutation of the β-globin gene was not associated with the thalassemic phenotype previously described. [ABSTRACT FROM PUBLISHER]

The aim of the present study was to report the use of analysis of fetal blood in prenatal diagnosis (PND) of β- and α-thalassemia (β- and α-thal), at a Chinese tertiary, maternity center. All cases undergoing invasive testing for PND of thalassemias from 1 January 2010 to 31 December 2014 were included. The main clinical characteristics of these invasive procedures were retrieved from the database software used for analysis. One thousand, nine hundred and six invasive PNDs were carried out for thalassemia, including 904 cases for β-thal and 1002 for α-thal. In the 904 PNDs for β-thal, chorionic villus sampling (CVS) was done in 321 cases and amniocentesis in 583 cases. No fetal blood analysis was used for cases at-risk for β-thal. In the 1002 PNDs for α-thal, CVS was done in 724 cases, amniocentesis in 137 cases and fetal blood analysis in 141 cases. All the 278 cases sampled by amniocentesis or fetal blood analysis were found to be affected by Hb Bart’s (γ4) disease. Currently, fetal blood analysis is considered only in relatively late gestation when Hb Bart’s disease has already been identified by ultrasound in a fetus at-risk for α-thal. [ABSTRACT FROM PUBLISHER]

α-Thalassemia (α-thal) is a common inherited disease in southern China. The severest form is Hb Bart’s (γ4) disease, in which the affected fetuses almost always diein uteroor shortly after birth, and the mothers are at high risk for severe morbidity. The most common type of α0-thalassemia (α0-thal) in southern China is Southeast Asian (– –SEA) deletion. Occasionally, Hb Bart’s disease, caused by a compound heterozygosity for the – –SEAand – –THAIα0-thal deletions, can also be encountered. In this study, we report our experience with the prevention of Hb Bart’s disease associated with the – –THAIα0-thal deletion. A total of 385 couples at risk for Hb Bart’s disease, including seven who tested positive for the – –SEAdeletion in one partner and the – –THAIdeletion in the other, were found. Different prenatal procedures were offered, depending on the gestational age at presentation. Sixty-six affected fetuses were diagnosed prenatally; among these, two cases of Hb Bart’s disease were compound heterozygotes for the – –SEAand – –THAIdeletions. All affected pregnancies were terminated in time. We also presented a diagnostic protocol for identification of α0-thal trait that can reduce the number of samples for detection of the – –THAIdeletion. [ABSTRACT FROM AUTHOR]

α+-Thalassemia (α+-thal) is common in Southern China. The high frequency could be due to over dominant selection through malaria. Two molecular mechanisms that produce α+-thal have been defined; one results in the –α3.7(rightward) deletion and reciprocal αααanti 3.7triplication, and the other one results in the –α4.2(leftward) deletion and reciprocal αααanti 4.2triplication. Considering that eachde novoevent produced a chromosome with an α gene deletion and a chromosome with an α triplication, if there is no favorable allele, one would expected to find the same allelic frequencies. We found a favorable selection for the –α3.7deletion in the Chinese population, and we also found that the α triplication is not as rare as was first thought, especially for the αααanti 3.7triplication. [ABSTRACT FROM AUTHOR]

Hb Quong Sze [Hb QS, HBA2: c.377T > C (or HBA1)] is a common nondeletional thalassemia in southern China. It is one of the major alleles causing nondeletional Hb H (β4) disease in the Chinese population. There is no strategy currently in place that aims to screen using hematological index cutoffs for this variant. This study was carried out to evaluate whether it is effective to use mean corpuscular hemoglobin (MCH) <27.0 pg as a screening test in the first step of screening for Hb QS carriers in southern China. The data of hematological testing in the Hb QS carriers obtained from couples who underwent prenatal thalassemia screening, regardless of the red blood cell (RBC) indices, were retrospectively reviewed. A total of 51 Hb QS carriers were identified, giving a prevalence rate of 0.2%; among these, 45 were Hb QS heterozygotes. The values of hemoglobin (Hb), MCV and mean corpuscular Hb (MCH) in the 45 Hb QS heterozygotes were 13.2 ± 1.8 g/dL, 75.2 ± 3.3 fL and 24.5 ± 0.5 pg, respectively. Eight heterozygotes (17.8%) had an MCV value of >80.0 fL, ranging from 80.9 to 84.1 fL, and would not be detected using the cutoff value of MCV <80.0 fL as a criterion for thalassemia screening. However, if screening had been based on the MCH <27.0 pg value, all 45 Hb QS heterozygotes would have been detected. Using a cutoff value of MCH <27.0 pg in nondeletional thalassemia screening would greatly decrease the DNA diagnosis burden. [ABSTRACT FROM AUTHOR]

We have identified a new β chain hemoglobin (Hb) variant in a Chinese individual. Sequencing of the β-globin gene revealed a mutation in exon 2 at nucleotide 271, which results in the replacement of a glutamic acid by glutamine at codon 90 [β90(F6)Glu → Gln; GAG > CAG; HBB: c.271G > C] that we have named Hb Henan. [ABSTRACT FROM AUTHOR]

Hb H (β4) disease is an inherited hemoglobin (Hb) defect in which three of the four α-globin genes are deleted or dysfunctional. The clinical manifestations vary widely from mild asymptomatic anemia to a severely anemic state. Recent literature suggests that Hb H disease is not as benign a disorder as previously thought. Newborn screening for Hb H disease is especially appealing because the screening test is based on the detection of Hb Bart's (γ4) that is only possible within the newborn period. In a 2-year period of newborn screening, 18 babies were found to have Hb H disease in a total of 9490 newborns. The overall prevalence for Hb H disease among all newborns in southern China is approximately 1 in 500. The correct diagnosis would allow affected infants to be properly cared for and reduce mortality rate. [ABSTRACT FROM AUTHOR]

Thalassemia screening usually involves cut-off values based on a mean corpuscular volume (MCV) of less than 80 fL or a mean corpuscular hemoglobin (MCH) of less than 27 pg. These strategies are able to detect almost all heterozygous carriers of the α-thalassemia (α-thal) (- -SEA) deletion in the Chinese population. However, an exception can occur. We describe an α0-thal trait with normal red cell indices in two Chinese individuals. [ABSTRACT FROM AUTHOR]

A G>C substitution at position 479 of the Gγ-globin gene results in a glutamic acid to glutamine substitution at codon 101 of the Gγ-globin chain, a new γ chain variant that we have named Hb F-Zhejiang [Gγ101(G3)Glu→Gln]. [ABSTRACT FROM AUTHOR]

Coinheritance of δ-globin variants along with β-globin gene defects can interfere with correct diagnosis of β-thalassemia (β-thal) trait. In this report, we present the coinheritance of a δ-globin variant, Hb A2-Tianhe [δ107(G9)Gly→Asp;HBD: c.323G>A] and a heterozygous β-thal in a Chinese individual with microcytosis, hypochromia and a normal Hb A2level. [ABSTRACT FROM AUTHOR]

Mutations that cause destabilization of the hemoglobin (Hb) tetramer are a rare cause of hemolytic anemia. In contrast to the hemolytic anemia caused by enzyme deficiencies, a dominant mode of inheritance characterizes the unstable Hbs. Hb Alesha [β67(E11)Val→Met;HBB: c.202G>A] is caused by a G>A mutation at codon 67 of the β-globin gene, resulting in a valine to methionine substitution at helix E11. This replacement disrupts the apolar bonds between valine and the heme group, producing an unstable Hb and severe hemolysis. We report this rare hemoglobinopathy in a Chinese girl with severe hemolytic anemia, splenomegaly and frequent requirement for red blood cell (RBC) transfusions. [ABSTRACT FROM AUTHOR]

An elevated Hb A2(α2δ2 level) is a diagnostic marker for heterozygous β-thalassemia (β-thal). Mutations in the δ-globin gene can cause decreased expression of Hb A2, compromising screening for heterozygous β-thal. In this report, we describe a novel missense mutation of the δ-globin [Hb A2-Fengshun or δ121(GH4)Glu→Lys,HBD: c.364G > A] in a Chinese individual who had coinherited a heterozygous β-thal with a normal Hb A2level. [ABSTRACT FROM AUTHOR]

We present the first description of a novel β-thalassemia (β-thal) mutation in a Chinese family. This mutation is located at −27 of the TATA box in the promoter of the β-globin gene (HBB: c.-77A > G) and is likely associated with a phenotype of β+-thalassemia (β+-thal). [ABSTRACT FROM PUBLISHER]

We report a rare mutation, HBA2: c.184A>T on the α2-globin gene, detected in a Chinese proband who presented with Hb H disease and a mild anemia. This frameshift mutation results in a premature termination of translation at position 61 of the α2-globin gene. Carriers of this mutation showed a borderline microcytic hypochromia. Our study indicates the importance of screening nondeletional α-thalassemia (α-thal) in areas with a particularly high prevalence of thalassemia such as in Southern China, especially for couples with one partner carrying an α0-thal deletion. [ABSTRACT FROM AUTHOR]

We describe a new α-globin chain variant in a Chinese subject. This novel variant, with a Val→Met substitution at codon 93 of the α-globin chain, has been named Hb Qingcheng (HBA1: c.280G>A) for where the proband was born. A woman with somatic mosaicism for Hb Qingcheng presented with the phenotype of mild α-thalassemia (α-thal). [ABSTRACT FROM AUTHOR]

We have found an example of the mutation at the intronic region of the second intervening sequence of the β-globin gene, IVS-II-705 (T>G) (HBB: c.316-146T>G), in a Chinese family. The two subjects heterozygous for this mutation presented with typical β-thalassemia (β-thal) trait. [ABSTRACT FROM AUTHOR]

We describe a new β-thalassemic mutation in a Chinese subject. This allele develops by insertion of one nucleotide (+T) between codons 138 and 139 in the third exon of the β-globin gene. The mutation causes a frameshift that leads to a termination codon at codon 139. In the heterozygote, this allele has the phenotype of classical β-thalassemia (β-thal) minor. [ABSTRACT FROM AUTHOR]