Epidemiological Survey of Hemoglobinopathies Based on Next-Generation Sequencing Platform in Hunan Province,China

Objective This study was aimed at investigating the carrier rate of,and molecular variation in,α-andβ-globin gene mutations in Hunan Province.Methods We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province.Hematological screening was performed,and molecular parameters were assessed.Results The overall carrier rate of thalassemia was 7.1%,including 4.83%forα-thalassemia,2.15%forβ-thalassemia,and 0.12%for bothα-andβ-thalassemia.The highest carrier rate of thalassemia was in Yongzhou(14.57%).The most abundant genotype ofα-thalassemia andβ-thalassemia was-α^(3.7)/αα(50.23%)andβ^(IVS-Ⅱ-654)/β^(N)(28.23%),respectively.Fourα-globin mutations[CD108(ACC>AAC),CAP+29(G>C),Hb Agrinio and Hb Cervantes]and sixβ-globin mutations[CAP+8(C>T),IVS-Ⅱ-848(C>T),-56(G>C),beta nt-77(G>C),codon 20/21(-TGGA)and Hb Knossos]had not previously been identified in China.Furthermore,this study provides the first report of the carrier rates of abnormal hemoglobin variants andα-globin triplication in Hunan Province,which were 0.49%and 1.99%,respectively.Conclusion Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population.The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.

Abnormal hemoglobins found in Hunan

To summarize the results of general survey, primary structure analysis and related functional studies of abnormal hemoglobins (Hbs) found in Hunan Province Data sources International Hb journals, Chinese biochemical and biomedical journals and other articles relevant to hematology Study selection All Hb variants found in Hunan and identified by primary structure analysis during 1980-1991 were included Data extraction Data concerning 11 types of Hb variants found in 3 districts and 7 counties in Hunan Province were briefly documented Their frequencies of occurrence were calculated and their distributions among Han, Yao, Tujia and Dong ethnic groups were listed Results Thirty six cases with abnormal Hb were identified out of 7412 individuals screened in Hunan 11 different types of Hb variants were recognized by primary structure analysis in 19 propositi along with their family members, including 5 α chain variants, 4 β chain variants, 1 δ chain variant and 1 δ β chain fusion variant Oxygen equilibrium characteristics, reaction dynamics, the rate of globin chain synthesis (RGCS), morphology observation by electron microscopy and DNA analysis were all used in the functional studies of hemoglobinopathies Conclusions The average incidence of abnormal Hbs in Hunan is 0 486% In Jianghua County, whose inhabitants are mostly of the Yao ethnic group, the incidence is significantly higher (1 09%) Hb Jianghua [β120(GH3) LysIle] and Hb Shuangfeng (SF)[α27(B8) GluLys] were two new variants first reported in international literature; whereas Hb Lille [α74(EF3) AspAla], HbA 2 Flatbush [δ22(B4) AlaGlu] and Hb Lepore Boston [δ87(F3) β116(G18)] were the first three instances to be found in China Hb SF displayed an oxygen affinity 1 5 fold higher than that of HbA at pH 7 4 and 25℃ with its oxygen equilibrium curve shifted to the left Reticulocytes of Hb SF heterozygote showed unbalanced RGCS, quite similar to that found in β thalassemia minor Erythrocytes of Hb SF heterozygote were changed to spherocytes and began to lyse after incubation with sodium salicylate or sulfadiazine (pH 7 4, 37℃) for 2-4 h These findings explained the sudden attack of hemolytic anemia provoked by two drugs in Hb SF propositus The genotype of a patient with Hb Q H disease is identified as , / ,α Q by DNA restriction mapping

Incidence of Sickle Cell Disease and Other Hemoglobinopathies in Burkina Faso: Results of a Five-Year Systematic Neonatal Screening (2015-2019) in Four Urban Hospitals

Hemoglobinopathies, mainly Sickle cell disease (SCD), are the most common monogenic disorders in Africa. In Burkina Faso, data on these diseases are scarce, mainly hospital-based in Ouagadougou and its surroundings. In order to assess the incidence and allelic frequencies of the main hemoglobinopathies in newborns in Burkina Faso, we conducted a cross-sectional study from 2015 to 2019 in four hospitals. The study included babies of both sexes, regardless of ethnic group and parents’ hemoglobin status. It was a newborn screening and hemoglobin variants were detected using isoelectric focusing on cord blood samples and confirmed using hemoglobin electrophoresis by high-performance liquid chromatography. The proportions and cumulative incidences of the different hemoglobinopathies were computed. Hardy-Weinberg equilibrium law was applied to calculate genotypic and allelic frequencies. The significant level was p < 0.05. Out of 11,337 newborns included, 47.8% were males and 60.2% were from Bobo-Dioulasso. Abnormal hemoglobin was found in 27.1%, representing a cumulative incidence of 1:4 newborns. The incidence of SCD was 1.9% (1:53 newborns) with 27.9% of homozygous SS. Homozygous CC and compound heterozygous Cβ-Thalassemia accounted for 1.1%. SCD cases were 1.51 times higher in Bobo-Dioulasso (OR = 1.51;95% CI [1.09 - 2.10]: p = 0.013). The observed genotype frequencies were significantly different from the expected ones (p 0.001). The βS and βC alleles represented 5.1 and 9.9%, respectively. This study showed a high incidence of hemoglobinopathies. Such results raise the question of control strategies for these hemoglobinopathies in our country.