Prevalence and molecular spectrum of α- and β-globin gene mutations in Hainan, China

Abstract

Background: Thalassemia is one of the most prevalent inherited single gene diseases. Prevention of βthalassemia through prenatal diagnosis is the one of the most effective and direct approach to control the spread of this life-threatening disease. This study aims to determine the prenatal diagnosis of αthalassemia and β-thalassemia in 3049 families among eighteen regions of Hainan Province using molecular diagnosis.Methods: This study enrolled a total of 3049 couples and their fetuses at The First A liated Hospital of Hainan Medical University from January 2004 to March 2020. Genomic DNA was extracted from peripheral blood of the couples and villus, amniotic uid, or fetal cord blood of fetuses. DNA-based diagnosis was performed using polymerase chain reaction.Results: Here, the most commonly detected mutation of α-thalassemia was a South-East Asian deletion (31.53%), followed by -α 4.2 /αα (11.15%), -α 3.7 /αα (11.02%). The most common mutation for βthalassemia was CD41/42, followed by -28, accounting for 30.27% and 2.56%, respectively. The regions with the highest prevalence were the coastal regions and the regions with the lowest prevalence were Wenchang, Lingao and Ding'an. We also examined thalassemia gene mutations in Han people and other minority groups and found that the most common gene mutations in different ethnic were not homogeneous. Prenatal diagnosis showed 556 normal, 118 α-thalassemia hydrops and 161 βthalassemia major fetuses. Conclusion:Our ndings provide important information for clinical genetic counseling of prenatal diagnosis for thalassemia major in Hainan Province. Methods SubjectsThis study included pregnant women and their husbands who registered for a program of diagnosis of thalassemia at The First A liated Hospital of Hainan Medical University in Hainan Province between January 2004 and March 2020. All couples had resided in Hainan Province, and came from eighteen regions including Haikou,

Molecular Spectrum, Ethnic and Geographical Distribution of Thalassemia in the Southern Area of Hainan, China

“…Ethnic differences may also play a significant role in genetic differences, so we also analyzed thalassemia genotypes in the Han and the minority ethnic groups. In the present study, 74.1% of -- SEA /αα carriers were the Han people, and 19.7% were the Li people, which is consistent with previous studies ( 11 , 28 ), indicating that the -- SEA /αα mutation is more common in the Han than the Li people.…”

“…The most common mutations are β CD41−42 , β CD17 , β IVS−II−654 , β −28 M , β CD71−72 , β −26 M , β IVS−I−1 , and β −29 M , and these mutations account for more than 95.0% of all β mutations found in the Chinese population ( 29 ). In the current study, 13 genotypes were detected, and β CD41−42 /β N (69.6%) was the most common β-thalassemia genotype in the southern part of Hainan, which was similar to that in an earlier study ( 28 ) and different from that in another study ( 11 ). The proportion of β CD41−42 (88.0%) among β-thalassemia in the southern part of Hainan was the highest and was higher than those in other provinces of China ( 12 , 16 , 17 , 30 ).…”

“…However, the -- SEA deletion was the most common α-thalassemia genotype in the southern region of China, such as Guangdong ( 14 , 25 ), Guangxi ( 18 , 19 , 23 , 24 , 26 ), Yunnan ( 20 , 22 ), Sichuan ( 13 ), Jiangxi ( 17 ), Hubei ( 16 , 21 ) and Hunan Province ( 27 ). Wang et al ( 11 ) reported that -- SEA /αα was identified in 39.1% of α-thalassemia mutation carriers in Hainan. However, -- SEA /αα was identified only in 6.0% of all α-thalassemia mutation carriers in the southern area of Hainan.…”

“…Furthermore, with economic improvement and population migration, thalassemia is spreading to all parts of China, including all parts of Hainan. Only a few studies have reported the prevalence rates and mutations associated with α- and β-thalassemia in this region ( 9 – 11 ), and the current epidemiological characteristics (molecular spectrum, ethnic, and regional) of thalassemia are not completely understood.…”

Genetic correction of concurrent α- and β-thalassemia patient-derived pluripotent stem cells by the CRISPR-Cas9 technology

“…In Southern China, α-thalassemia and β-thalassemia are the main two types observed [ 4 ]. It was reported that the most commonly detected mutation for α-thalassemia was SEA/αα (31.53%); the most common mutation for β-thalassemia was CD41/42 (30.27%) in Hainan province, southernmost China [ 5 ]. The clinical phenotypes of concurrent α- and β-thalassemia depend on how many of the four genes for α globin or two genes for β globin are missing [ 6 ].…”