Molecular Epidemiological Investigation of Thalassemia in the Chengdu Region, Sichuan Province, Southwest China

Abstract

Thalassemia is the most common inherited disease in southern China. However, this disorder is usually ignored by the health system in the Sichuan Province due to the lack of epidemiological data. To provide basic epidemiological data for thalassemia screening, genetic counseling, and prenatal diagnosis (PND) in the Chengdu region, a total of 3262 healthy subjects were assessed by complete blood count (CBC), reverse dot-blot gene chip, gap-polymerase chain reaction (gap-PCR), and PCR-DNA sequencing. A frequency of heterozygous thalassemia of 3.43% (112/3262) was found, of which 2.21% (72/3262) patients carried α-thalassemia (α-thal), 1.19% (39/3262) β-thalassemia (β-thal) and 0.3% (1/3262) hereditary persistence of fetal hemoglobin (Hb) (HPFH)/δβ-thalassemia (δβ-thal). Four types of α-thal mutations were found, the most prevalent being - -(SEA) (68.06%), followed by -α(3.7) (rightward deletion, 25.0%), Hb Quong Sze (Hb QS; HBA2: c.377 T > C) (4.17%), and -α(4.2) (leftward deletion, 2.78%). The seven β-thal mutations included: codons 41/42 (-TTCT), HBB: c.126_129delCTTT (13/39, 33.33%); codon 17 (A > T), HBB: c.52 A > T (11/39, 28.95%); IVS-II-654 (C > T), HBB: c.316-197 C > T (9/39, 23.68%); -28 (A > G), HBB: c.-78 A > G (3/39, 7.69%); -29 (A > G), HBB: c.-79 A > G (1/39, 2.56%); codons 27/28 (+C), HBB: c.84_85insC (1/39, 2.56%), and the rare IVS-II-850 (G > T), HBB: c.316-1 G > T (1/39, 2.56%). Only one case of the Southeast Asian HPFH deletion was found. This is the first detailed molecular epidemiological survey of thalassemia in the Chengdu region, Sichuan Province, People's Republic of China (PRC).

Prevalence and Molecular Spectrum of α- and β-Globin Gene Mutations in Hainan, China

“…In our study, the prevalence of thalassemia carrier status in Sanya City was lower than that reported by Li [19]. Among α-thalassemia genotypes,-SEA/αα, which is consistent with the previous research by Sanya City and Ding'an County of Hainan Province, Sichuan, Fujian, Guangdong and Guangxi [19,20,15,5,3,9], but different from that of Lingshui Autonomous County of Hainan…”

Molecular analysis of α-thalassemia and β-thalassemia in Quanzhou region Southeast China

“…IVS-II-654 (C>T) was the most frequent β-thalassemia mutation with an allele frequency of 36.38%, followed by CD41-42 (-TCTT) (29.64%), which was similar to the results reported in Fujian,21 Taiwan22 and Jiangxi10 provinces. While, the most common β-thalassemia mutation was CD41-42 (-TCTT) in other regions, such as Guangdong,11 Zhejiang,12 Guangxi,2 Sichuan13 provinces. Additionally, CD17 (A>T) was the most common β-thalassemia mutation in Guizhou province of South China 14.…”

“…Gap-PCR was used to detect the deletions of α-thalassaemia mutation (-α 3.7 , -α 4.2 , -- SEA ) 10–12. The PCR reverse dot blot hybridisation technique was used to detect the non-deletion α-thalassaemia mutations (Hb CS, Hb QS and Hb Westmead), and 17 common β-thalassaemia mutations,13–15 including CD41-42 (-TCTT), IVS-II-654 (C>T), –28 (A>G), CD71/72 (+A), CD17 (AAG >TAG), CD26 (GAG >AAG), CD43 (GAG >TAG), –29 (A>G), CD31 (-C), –32 (C>A), IVS-I-1 (G>T), CD27/28 (+C), –30 (T>C), CD14/15 (+G), Cap+40–43 (–AAAC), initiation codon (ATG >AGG) and IVS-I-5 (G>C).…”

The prevalence of thalassemia in mainland China: evidence from epidemiological surveys

“…However, due to a lack of a comprehensive system for data collection and analysis, there are no data on the precise frequency and distribution patterns, overall burden, and trends of α- and β-thalassemia at a national scale. Furthermore, with economic improvement and population migration, thalassemia is spreading to parts of China that are north of the Yangtze River 11 . The current epidemiological characteristics of thalassemia are not completely understood.…”