Xing-Mei Xie

Co-inheritance of α-thalassaemia and β-thalassaemia in a prenatal screening population in mainland China

Objective To determine the prevalence of α-thalassaemia in β-thalassaemia individuals in a Chinese population. Methods The standard diagnostic marker for β-thalassaemia was elevation of the Hb A2 level (>3.5%) with low mean corpuscular volume. The common α-thalassaemia mutations were studied by molecular analysis in all identified β-thalassaemia carriers. Results A prevalence rate of 3.3% for β-thalassaemia was found in our population; α- and β-thalassaemia interactions were found to co-exist in 17.8% of the β-thalassaemia carriers. The -SEA deletion was the most common α-thalassaemia mutation co-inherited with β-thalassaemia, followed by the -α3.7 deletion, the -α4.2 deletion, Hb Quong Sze, and Hb Constant Spring. Conclusion Our results suggest that it could be valuable to study co-existing α-globin mutations in subjects with β-thalassaemia trait in a prenatal screening programme, especially in populations with a high prevalence of haemoglobinopathies.

Screening for common β‐globin gene cluster deletions in Chinese individuals with increased hemoglobin F

The aim of this study was to determine the prevalence of β‐globin gene cluster deletions in individuals with increased Hb F levels in a Chinese population.

Consequences of Delayed Prenatal Diagnosis of β-Thalassemia in Mainland China.

Abstract β-Thalassemia (β-thal) is one of the most common inherited single gene disorders in the world. The aim of this study was to describe the gestational age at prenatal diagnosis (PND) for β-thal in at-risk women in mainland China. All pregnant women at-risk for β-thal and undergoing PND at a Mainland Chinese tertiary obstetric center between January 2005 and December 2014 were included. Information required for the survey was obtained from prenatal records and delivery charts. In total, 1307 women underwent PND for β-thal. The mean gestational age for the procedure was 18.5 weeks. There were 384 (29.0%) women with fetal diagnosis in early trimester (<14 weeks), 715 (55.0%) in early second trimester (14–24 weeks), and 208 (16.0%) in late second trimester or beyond (>24 weeks). Although the proportion of patients undergoing early PND increased along with the time span, the mean n gestational age was not decreased significantly during the study period. The delay in PND deprived couples of the opportunity to make informed decisions early in pregnancy.

Hydrops Fetalis Associated with Compound Heterozygosity for Hb Zurich-Albisrieden (HBA2: C.178G > C) and the Southeast Asian (– –SEA/) Deletion

Abstract Hb Zurich-Albisrieden [HBA2: c.178Gu2009>u2009C; 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 5.5u2009g/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 – –SEA α0-thal deletion, and the fetus was a compound heterozygote for Hb Zurich-Albisrieden and the – –SEA α0-thal deletion. Therefore, this was a rare case of Hb Bart’s hydrops fetalis associated with Hb Zurich Albisrieden.

Implementation of Newborn Screening for Hemoglobin H Disease in Mainland China

Hemoglobin H disease is the most severe non-fatal form of α-thalassemia syndrome characterized by pronounced microcytic hypochromic hemolytic anemia. It is predominantly seen in Southeast Asia, the Middle East and the Mediterranean. Studies suggest that hemoglobin H disease is not as benign a disorder as previously thought. Newborn screening for hemoglobin H disease is especially appealing because the screening test is based on the detection of hemoglobin Bart’s (γ4) that is only possible within the newborn period. In this study, we reported on a 4-year period of newborn screening program at a mainland Chinese hospital, which detected 35 babies with hemoglobin H disease in a total of 26 152 newborns. The overall prevalence for hemoglobin H disease among all newborns in southern China is ~1 in 1,000. These children need appropriate follow-up and potential comprehensive care during their growth and development.

A New Hemoglobin Variant: Hb Henan [β90(F6)Glu → Gln; HBB: c.271G < C]

Abstract 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)Gluu2009→u2009Gln; GAGu2009>u2009CAG; HBB: c.271Gu2009>u2009C] that we have named Hb Henan.

Diagnostic Dilemma of Hb Perth [β32(B14)Leu→Pro; HBB: c.98T > C] in Mainland China.

Abstract Unstable hemoglobin (Hb) variants represent a rare etiology of congenital hemolytic anemia. Correct diagnosis can be a challenge due to the relative rarity or lack of awareness of this disorder. We report an 18-month-old girl, who presented with a long-standing hemolytic anemia. Her diagnosis of unstable Hb Perth [β32(B14)Leu→Pro, HBB: c.98Tu2009>u2009C] had not been made until gene sequencing of the β-globin gene was performed.

Neonatal screening for α‐thalassemia by cord hemoglobin Barts: how effective is it?

It has long been recognized that the hemoglobin (Hb) Barts in cord blood is an accurate indicator of α‐thalassemia and that the level of Hb Barts was increased accordingly with the increasing numbers of the defective α‐genes.

Heterozygous β-thalassemia with complete absence of hemoglobin A2 in a Chinese adult.

Heterozygous b-thalassemia with complete absence of hemoglobin A2 in a Chinese adult Sir, b-thalassemia is caused by the reduced (b) or absent (b) synthesis of the b-globin chains of the hemoglobin (Hb) tetramer, which is made up of two a-globin and two b-globin chains (a2b2). Carriers of b-thalassemia are clinically asymptomatic. The characteristic hematological features are microcytosis, hypochromia, and increased HbA2 (a2d2). In a thalassemia endemic region, if both partners of a couple are defined carriers for b-thalassemia, each of their offspring has a 25% risk of being affected by homozygous b-thalassemia, which is a severe transfusion-dependent anemia. Therefore, carrier screening is extremely useful by allowing couples at risk to make informed decision on their reproductive choices. Through genetic counseling and the option of prenatal testing, such a couple can opt to bring to term only those pregnancies in which the fetus is unaffected. Elevation of HbA2 is the most important feature in the detection of heterozygous b-thalassemia, but there are sometimes bthalassemia heterozygotes with normal HbA2, compromising the screening effectiveness [1–5]. b-thalassemia with the absence of HbA2 is very rare. We herein report such a case in a Chinese adult during our prenatal thalassemia screening program.

A New δ-Globin Gene Variant: Hb A2-Fengshun [δ121(GH4)Glu→Lys (HBD: c.364G > A)].

Abstract 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.364Gu2009>u2009A] in a Chinese individual who had coinherited a heterozygous β-thal with a normal Hb A2 level.