Jian-Ying Zhou

Prenatal control of nondeletional α-thalassemia: first experience in mainland China

To demonstrate the performance of nondeletional α‐thalassemia prevention at a mainland Chinese hospital.

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.

Maternal serum ADAM12 in Chinese women undergoing screening for aneuploidy in the first trimester.

Objective.u2003To evaluate the potential of maternal serum using a disintegrin and metalloprotease 12 (ADAM12) as a marker for Trisomy 21 in Chinese pregnant women. Methods.u2003Serum samples were collected and stored from women having a viable singleton pregnancy undergoing first trimester screening for Trisomy 21 between 2006 and 2007. Serum concentration of ADAM12 was measured using an automated time-solved immuno-fluorometric assay from 608 stored serum samples (601 Euploidy and 7 Trisomy 21). Regression analysis was used to determine the expected median in Euploidy pregnancies after adjusting for pregnancy characteristics. The level of ADAM12 MoM was compared between Trisomy 21 and Euploidy pregnancies. Expected median levels in Chinese were compared to that published for Caucasians and Afro-Caribbeans. Results.u2003In Euploidy pregnancies, the concentration of ADAM12 increased with CRL and decreased with maternal weight. The expected median level of ADAM12 in Chinese was significantly lower than Caucasian and Afro-Caribbeans (Fu2009=u200914.2, pu2009<u20090.0001). There was a significant correlation between log10ADAM12 MoM both log10 pregnancy-associated plasma protein A MoMs (ru2009=u20090.46; pu2009<u20090.001) and log10free βhCG MoMs (ru2009=u20090.08; pu2009=u20090.048). The median ADAM12 MoM in Trisomy 21 pregnancies was not significantly different from that in Euploidy pregnancies (zu2009=u20090.18; pu2009=u20090.88). Conclusion.u2003ADAM12 concentrations in Chinese are lower than those of Caucasians and Afro-Carribeans; that ADAM12 MoM levels in Euploidy and Trisomy 21 pregnancies were not statistically different.

First Case of a Compound Heterozygosity for Two Nondeletional α-Thalassemia mutations, Hb Constant Spring and Hb Quong Sze

Abstract 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.427Tu2009>u2009C) 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.377Tu2009>u2009C) 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.

KFL1 Gene Variants in α-Thalassemia Individuals with Increased Fetal Hemoglobin in a Chinese Population

Abstract Krüppel-like factor 1 (KLF1) is a pleiotropic erythroid transcription factor that is a regulator of definitive erythropoiesis. The aim of this study was to detect KLF1 gene variants in α-thalassemia (α-thal) carriers with an increased Hb F level in a Chinese population, and determine the changes of hematological parameters as a result of interactions between KLF1 gene mutations and α-thal. Subjects with α-thal and Hb F levels of ≥1.0% were selected for further investigation. Direct sequencing was used to detect KLF1 gene mutations. Hematological parameters of subjects with α-thal and concomitant KLF1 gene mutations and those with α-thal alone were compared. The KLF1 gene variants were detected in 46 of 275 (16.7%) individuals with α-thal and Hb F levels of ≥1.0%. The detection rate of KLF1 gene mutations rose correspondingly when the Hb F level increased. For α0-thal carriers, significantly lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) values were observed in KLF1 gene mutation-positive carriers than that in KLF1 gene mutation-free carriers; conversely, significantly higher Hb A2 and Hb F levels were observed in the former condition rather than in the latter condition. The results of this study indicate that KLF1 gene variants are common in Chinese subjects with α-thal and increased Hb F levels, and KLF1 gene mutations decreased the red blood cell (RBC) indices in α-thal carriers as that in normal adults.

Analysis of the Genotypes in a Chinese Population with Increased Hb A2 and Low Hematological Indices

Abstract Increased Hb A2 is considered the most reliable hematological finding for the identification of β-thalassemia (β-thal) carriers. The aim of this study was to determine the underlying genetic factors associated with a high Hb A2 level in a Chinese population. Subjects were recruited from couples preparing for pregnancy who participated in the thalassemia screening program during a 2-year period. DNA analyses were used for diagnosis of β-thal and other genetic factors. A total of 5985 adults who screened positive for β-thal were recruited. Of these, 5933 (99.1%) were detected to have a β-thal mutation. In the remaining 52 (0.9%) individuals without mutations involving the β-globin gene cluster, 16 were found to have Krüppel-like factor 1 (KLF1) gene variants, and two had an α-globin gene triplication. There were still 34 individuals with unknown genetic factors for their raised Hb A2 values. The results of this study indicate that genetic factors other than β-thal can rarely contribute to the elevation of Hb A2. These subjects usually have borderline microcytic red cell indices and Hb A2 values.

Combination of Hb Heze [β144(HC1)Lys→Arg; HBB: c.434A>G] and β0-Thalassemia in a Chinese Patient with β-Thalassemia Intermedia

Abstract We first report a novel β chain variant, Hb Heze [β144(HC1)Lys→Arg; HBB: c.434A>G], in a Chinese family. Heterozygous inheritance of the mutation results in a mild β-thalassemia (β-thal) phenotype, whereas compound heterozygosity of Hb Heze with β0-thal appears as the cause of β-thal intermedia (β-TI) in our case.

Hb A2-Tianhe (HBD: c.323G>A): First Report in a Chinese Family with Normal Hb A2-β-Thalassemia Trait

Abstract 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 A2 level.