Prevalence And Molecular Characterization Of Structural Hemoglobin Variants In The Dongguan Region Of Guangdong Province

Hemoglobinpathies were a kind of inherited hemoglobin disorders, which caused bygenetic defect that result in abnormal structure and quantitative of the globin chains. It can bedivided into two general types: the thalassemias and the hemoglobin variants: structural Hbvariants are typically due to point mutations in a globin gene that produces a single amino acidsubstitution in a globin chain; thalassemias, in contrast, result from quantitativeunderproduction of globin chains, usually produce clinical manifestations such as hemolyticanemia, like α-、β-or δ-thalassemia. According to statistics, the inherited hemoglobinpathiesare the most common monogenetic diseases and approximately7%of the world population arecarriers of such disorders. Hemoglobinpathies were mainly characteristic of the tropics andsubtropics, and in south China was high frequency region, especially in Guangdong andGuangxi. According to the previous reports, the frequency of α-thalassemia and β–thalassemiarespectively was8.19%and2.54%in Guangdong province. However, there have been only afew epidemiological studies of structural Hbs in this area. Previous studies have found thatmost of hemoglobin Variants don’t change in physiological function, but a few will have achange and lead to clinical symptoms, the most common is hemolytic anemia. Patients willsuffer moderate to severe anemia, especially when hemoglobin variants compoundαor βthalassemias. Until now, there was no effective treatment for hemoglobinopathies, some severecases rely on long-term transfusion, which brings huge economic burden to families and society.So it’s particularly important for screening hemoglobinopathies in high frequencies regions.Our research will be important implications for genetic counselling in a region at highfrequency of hemoglobin variants. Objective1. To investigate the prevalence of hemoglobin variants and frequencies of genotypes inDongguan Distrect.2. To explore the hematological characteristics and molecular characterization of abnormalHbs in the population of the Dongguan region.3. To explore the hematological traits when hemoglobin variants compound α or βthalassemia.Methods1. During Oct.2011to Sep.2013,30,848cases of peripheral blood of couples who came toprenatal clinic at Dongguan Maternal and Children Health Hospital for prenatal thalassemiascreening.2. All blood samples were sent for the determination of the hematological parameters and Hbelectrophoresis.3. For these samples with suspected abnormal Hbs, the α1and α2globin genes or β globingene were amplified by PCR and sequenced.4. For these samples with suspected abnormal Hbs,α thalassemia was be investigated further.Gap-PCR was used to determine the three common α globin gene deletion mutations(-α3.7,-α4.2,--SEA). PCR-reverse dot-blot was used to determine the three common α globingene nondeletional mutation (αCSα,α WSα, αQSα),and RDB was also used to determine the17common β globin gene mutations.5. Analysed, classified and statistics for the research results.Results1.131samples were identified with α1and α2globin or β globin variants from30,848unrelated partners, the gene frequency of abnormal Hbs is0.4%(131/30848). Among these,there are74samples with α globin variants and57samples with β globin variants.2. In Dongguan region, the most common variant was Hb CS(carrying rate0.2%)，accountedα globin variants for77%, followed by Hb Q-Thailand and Hb Honolulu; the most commonβ globin variants was Hb E (carrying rate0.09%), accounted β globin variants for50.9%,followed by Hb New York. 3. The hematological indices of Hb CS simple heterozygotes: Hb120.7±17.0g/L，MCV83.7±4.7fL， MCH27.4±2.1pg; The hematological indices of Hb E simpleheterozygotes: Hb126.4±17.9g/L，MCV78.3±3.9fL，MCH26.3±1.0pg.4. The hematological indices of Hb CS compound--SEA/αα thalassemia(Hb H-CS): Hb57.3±17.0g/L，MCV79.7±4.4fL，MCH19.4±2.2pg; the hematological indices of Hb CScompound--SEA/αα and β thalassemia: Hb93g/L，MCV50.3fL，MCH16.1pg. Thehematological indices of Hb E compound--SEA/αα thalassemia: Hb145g/L，MCV68.5fL，MCH23.2pg; the hematological indices of Hb E compound β thalassemia (CD41-42):Hb59g/L，MCV57.2fL，MCH16.7pg.5. After gene sequencing of the whole α globin gene or β globin gene, eight differentmutations of α globin variants（Hb CS、Hb Q-Thailand、Hb G-Honolulu、Hb Ottawa、Hb Queens、Hb Ube-2、Hb Beijing、Hb Arya）and six types mutations of β globin variants（Hb E、Hb New York、Hb J-Bangkok、Hb G-Taipei、Hb Maputo、Hb J-Kaohsiung）were identified. Among these, Hb Arya and Hb Maputo have not been reported yet inChinese.Conclusion1. The gene frequency of Hb variants is0.4%(131/30,848) in Dongguan region. This indicatesthat abnormal hemogolobins are likely not common in our population.2. In Dongguan region,the most common α globin variant was Hb CS (carrying rate0.2%),accounted α globin variants for77%; the most common β globin variants was Hb E(carrying rate0.09%), accounted β globin variants for50.9%.3. Due to a high frequency of Hb CS and α0-thalassemia（--SEA） in Dongguan, if one partnerhas been identified for--SEA/αα thalassemia, the other should be subjected to detailedscreening for hemoglobin variants, especially the Hb CS. As parts of the Hb E carriersMCV, MCH performance normal, for one partner detected with β0-thalassemia, the other,should be pay attention to β globin gene detection, especially the Hb E.