Objectives Thalassemia is a highly prevalent monogenic inherited disease in southern China. It is important to collect epidemiological data comprehensively for proper prevention and treatment. Methods In this study, blood samples collected from 15 807 residents of Chenzhou were primarily screened by hematological tests. A total of 3973 samples of suspected thalassemia carriers were further characterized by combined next-generation sequencing (NGS) and Gap-PCR. Results In total, 1704 subjects were diagnosed as thalassemia carriers with a total prevalence rate of 10.78%, including 943 α-thalassemia carriers, 708 β-thalassemia carriers, and 53 composite α and β-thalassemia carriers. The prevalence rates of α-thalassemia, β-thalassemia, and composite α and β-thalassemia were 5.97%, 4.48%, and 0.34%, respectively. Meanwhile, we characterized 19 α-thalassemia variations and 21 β-thalassemia variations in thalassemia carriers. Approximately 2.88% of thalassemia carriers would be missed by traditional genetic analysis. In addition, four novel thalassemia mutations and one novel abnormal hemoglobin mutation were identified. Conclusions Our data suggest a high prevalence of thalassemia and a diverse spectrum of thalassemia-associated variations in Chenzhou. Also, combined NGS and Gap-PCR is an effective thalassemia screening method. Our findings might be helpful for prevention and treatment of thalassemia in this region.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcla.22845

Next-generation sequencing improves molecular epidemiological characterization of thalassemia in Chenzhou Region, P.R. China.

Background: Thalassemia is an autosomal genetic disorder, found throughout the world. It is still not treatable and create socio economic problems. In this study, we investigated the prevalence and spectrum features of thalassemia in Yunnan Province, the southwestern area of China. During 2014-2018, a total of 3,539 suspected thalassemia children were detected with α- and β-thalassemia mutations by gap-Polymerase Chain Reaction (PCR) and reverse dot blot (RDB) analysis in Kunming Children's Hospital. Results: Of these patients, 1,130 were diagnosed thalassemia gene carriers with a carrying rate of 31.92%. Among them, α-thalassemia was 43.63%, β-thalassemia was 53.98%, cases with both α- and β- thalassemia was 2.39%. In α-thalassemia patients, the most common mutations was -SEA/αα (52.13%), followed by -α3.7/αα (27.79%), hemoglobin H disease (18.46%), and -α4.2/αα (1.62%). Fifteen gene mutations and 30 genotypes were identified in β-thalassemia patients, with the five most common mutations CD17 (A>T) (29.51%), CD41-42 (-TTCT) (27.87%), IVS-II-654 (C>T) (14.92%), CD26 (G>A) (6.89%), and CD26/CD27 (2.62%) accounting for 81.81% of the β-globin gene mutations. Furthermore, we founded two rare mutations CD34 (TGG → TAG) and Int in Chinese populations. Conclusions: Our results suggested that the prevalence and gene mutation spectrum of thalassemia display obviously heterogeneity among children in Yunnan Province. The findings provide the valuable information for premarital and pre-pregnancy screening, prenatal diagnostic services, and designing appropriate prevention programs to control thalassemia for future in this area.

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Gene Mutation Spectrum of Thalassemia Among Children in Yunnan Province.

Thalassemia is a group of inherited hemoglobic disorders resulting from defects in the synthesis of one or more of the hemoglobin chains, which is one of the most prevalent inherited disorders in southern China. Only few studies reported the molecular characterization of α- and β-Thalassemia in Hubei Province in the central of China. A total of 4889 clinically suspected cases of thalassemia were analyzed by Gap-PCR, PCR-based reverse dot blot (RDB). 1706 (33.8%) subjects harbored thalassemia mutations, including 539 (11.0%) subjects with α-thalassemia, 1140 (23.3%) subjects with β-thalassemia mutations, and 25 (0.51%) subjects with both α- and β-thalassemia mutations. Seven genotypes of α-thalassemia mutations and 29 genotypes of β-thalassemia mutations were characterized. --SEA/αα (66.05%), −α3.7/αα (24.12%), and -α4.2/αα (3.71%) accounted for 93.88% of the α-thalassemia mutations. βIVS-II-654/βN, βCD41–42/βN, βCD17/βN, βCD27–28/βN, βCD71–72/βN, β − 28/βN, β − 29/βN, βCD43/βN, βE/βN, accounting for 96.40% of all β-thalassemia genotypes. Furthermore, mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) were sensitive markers for both β-thalassemia and α-thalassemia with --SEA/αα, but not -α3.7/αα and -α4.2/αα. Conclusions: Our data indicated great heterogeneity and extensive spectrum of thalassemias in Hubei province of China.

/pdf/alpha-and-beta-thalassemia-mutations-in-hubei-area-of-china-4c9f378olt.pdf

Alpha and beta-Thalassemia mutations in Hubei area of China.

Thalassemia is one of the most common genetic diseases in southern China. Accurate population frequency data regarding the occurrence and distribution of thalassemia is important for designing appr...

Prevalence and genetic analysis of thalassemia in neonates in Wuhan area: a national megacity in central China.

Introduction Newborn screening is an important supplement to thalassemia control and prevention. Capillary electrophoresis (CE) technology has several advantages for thalassemia screening but with low sensitivity, especially for thalassemia carriers. This study aims to illustrate the application of an optimized interpretation model in newborn thalassemia screening by capillary hemoglobin electrophoresis. Methods Two thousand, two hundred fifty-eight neonates selected from four regions in China were enrolled and were screened for α-thalassemia and β-thalassemia by capillary electrophoresis. Results were interpreted based on an optimized model integrated with multiple parameters. Molecular analysis was carried out in synchrony and used as the gold standard for the screening performance assessment. The consistency among different regions and thalassemia genotypes were also investigated. Results Among the 2258 neonates, 485 were identified to have a likely diagnosis of thalassemia, and 422 α-thalassemia, 80 β-thalassemia, and 21 α/β-thalassemia cases were confirmed by molecular analysis, including 277 α-thalassemia silent carriers, 135 α-thalassemia trait carriers, 10 Hemoglobin H disease, and 80 β-thalassemia trait carriers. The screening sensitivity, specificity, positive, and negative predictive value for α-thalassemia and β-thalassemia were 84.83%, 99.14%, 95.98%, 96.41%, and 88.75%, 98.73%, 76.34%, and 99.48%, respectively. The optimized interpretation model showed higher performance for thalassemia carriers, though some neonates with silent α-thalassemia genotypes (-α3.7 /αα, -α4.2 /αα, and αWS α/αα) and β-28 /βN genotype were still missed. The screening performance among different regions was comparable. Conclusions Capillary hemoglobin electrophoresis with the optimized interpretation model shows reliable performance for newborn thalassemia screening. It is applicable to large-scale population screening.

Application of an optimized interpretation model in capillary hemoglobin electrophoresis for newborn thalassemia screening.

Hunan province located in the south of China has a high incidence of haemoglobinopathies. In the present study, we surveyed the accurate population frequency data of the local population in Changsha city of Hunan province in China. The data includes the carrying rate, gene mutation types and their distribution features for thalassaemia. In total, 7500 consecutive samples from five geographical areas of Changsha were analysed for both haematological and molecular parameters. Therewas a high prevalence of carriers of α-thalassaemia (2.57%), β-thalassaemia (1.9%) and both α-thalassaemia and β-thalassaemia (0.08%). Overall, 4.54% of the population in this area represented heterozygous carriers of α-thalassaemia and β-thalassaemia. The mutation spectrum of α-thalassaemia and β-thalassaemia and its haematological characterization were fully described for this area. The present study is the first to report the prevalence of thalassaemia in Hunan province population. Both α-thalassaemia and β-thalassaemia carriers are widely distributed in Changsha. The knowledge gained from the present study will allow for an estimation of the projected number of pregnant women at risk for thalassaemia, and the design of a screening strategy for the control of thalassaemia in Changsha.

Hanmei Li

Papers

Prevalence and spectrum of thalassaemia in Changsha, Hunan province, China: discussion of an innovative screening strategy