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

Abstract

<jats:sec><jats:title>Aims</jats:title><jats:p>Thalassemia is one of the most prevalent inherited disorders in south China. However, there still has no comprehensive research on molecular characterisation of α-thalassemia and β-thalassemia in the Quanzhou region of Fujian province, a city with high incidence of thalassemia in Southeast China.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A total of 11 668 cases were collected in Quanzhou region from January 2013 to June 2019. The deletions of α-thalassemia were detected by Gap-PCR, α-thalassemia and β-thalassemia mutations were detected by DNA reverse dot blot hybridisation. Rare thalassemia gene testing and DNA sequencing were performed to detect rare and novel thalassemia mutation for suspected rare thalassemia carriers.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Among 11 668 subjects, 4796 (41.10%) subjects were diagnosed with thalassemia. 3298 (28.27%) subjects were α-thalassemia carriers, 26 types of α-thalassemia mutations were identified, with the common α-thalassemia genotypes being --<jats:sup>SEA</jats:sup>/αα (71.47%), -α<jats:sup>3.7</jats:sup>/αα (17.13%) and -α<jats:sup>4.2</jats:sup>/αα (3.49%). 1407 (12.06%) subjects were β-thalassemia carriers, 18 types of β-thalassemia mutations were identified. The common five genotypes of β-thalassemia were β<jats:sup>IVS-II-654</jats:sup>/β<jats:sup>N</jats:sup> (36.53%), β<jats:sup>CD41-42</jats:sup>/β<jats:sup>N</jats:sup> (30.28%), β<jats:sup>CD17</jats:sup>/β<jats:sup>N</jats:sup> (17.13%), β<jats:sup>CD26</jats:sup>/β<jats:sup>N</jats:sup> (5.12%) and β<jats:sup>-28</jats:sup>/β<jats:sup>N</jats:sup> (4.62%). Additionally, 91 (0.78%) subjects with composite α-thalassemia and β-thalassemia were identified. Furthermore, 9 α-thalassemia and β-thalassemia gene mutations (CAP +40–43 (-AAAC), IVS-I-1 (G&gt;T), IVS-I-5 (G&gt;C), SEA-HPFH, CD53 (-T), CD37 (A&gt;G), −90 (C&gt;T), CD3 (T&gt;C), -α<jats:sup>6.9</jats:sup>) were identified for the first time in the region. Among them, CD53 (-T), CD37 (A&gt;G) and −90 (C&gt;T) mutations were identified for the first time in Fujian province. Moreover, CD3 (T&gt;C), -α<jats:sup>6.9</jats:sup> mutations were first identified in Chinese individual.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Quanzhou region of South China has high incidence of thalassemia mutations. In this study, several cases of rare thalassemia mutations have been identified, providing reference for clinical consultation. The completion of this study is of great significance to strengthen the prevention and control of thalassaemia in the Quanzhou region.</jats:p></jats:sec>

Molecular Characterization Analysis of Thalassemia and Hemoglobinopathy in Quanzhou, Southeast China: A Large-Scale Retrospective Study

“…Fujian province, which is located in Southeast China, also displays a high prevalence of thalassemia ( Xu et al, 2013 ; Huang et al, 2019 ; Zhuang et al, 2020a ). Quanzhou prefecture has the largest population in Fujian and possesses high population mobility, which may have led to greater diversity and complexity of thalassemia gene mutations.…”

Genetic research and clinical analysis of deletional Chinese Gγ+(Aγδβ)0 -thalassemia and Southeast Asian HPFH in South China

“…The SEA-HPFH heterozygotes have no clinical symptoms, and hematological parameters are in the normal range or in borderline level. The Chinese G γ + ( A γδβ) 0 -thalassemia has a deletion range of about 78.9 kb, including some A γ globin genes, all δ and β-globin genes and DNA sequences with regulatory functions far downstream of the β-globin gene [10]. However, few research focus on the clinical features on these two common types of thalassemia.…”

<p>Establishment and Evaluation of a Novel Method Based on Loop-Mediated Isothermal Amplification for the Rapid Diagnosis of Thalassemia Genes</p>

“…At present, deletions of α-thalassemia are detected by Gap-PCR and the αand β-thalassemia mutations are detected by DNA reverse dot blot (RDB). 2,19,20 Compared to these methods, the LAMP assay has many advantages such as high sensitivity, and simple and fast operation, and it does not need a special instrument. Furthermore, the cost of detecting thalassemia (include -SEA, -α3.7, and -α4.2 αthalassemia, and 654M, 41/42M, −28M, 17M, 27/28M β-thalassemia) using commonly clinical test kits is about 300 CNY in our hospital, while the cost of detecting thalassemia using the LAPM method in the manuscript is about 30 CNY.…”

“…13 In Quanzhou region of Southeast China, -SEA/deletion, -α3.7/deletion, and -α4.2/deletion are the most common β-thalassemia mutations whereas βIVS-II-654/βN, βCD41-42/βN, βCD17/βN, βCD26/βN, and β-28/ βN are the most common α-thalassemia mutations. 2 In Ganzhou, Jiangxi, -SEA/deletion, -α3.7/deletion, and -α4.2/deletion were the most common α-thalassemia mutations whereas 654M, 41/42M, −28M, 17M, and 27/28M were the most common β-thalassemia mutations. In this study, we aimed to design and evaluate a new method for detecting three αthalassemia mutations including -SEA, -α3.7, and -α4.2, and five β-thalassemia mutations including 654M, 41/42M, −28M, 17M, and 27/28M using LAMP.…”

“…At present, the deletions of α-thalassemia are detected by gap-polymerase chain reaction (PCR) and αand β-thalassemia mutations are detected by DNA reverse dot blot (RDB). 2 These methods have high requirements for space, instruments, and personnel, and it is difficult to promote their use in primary hospitals and rural areas. 3 Therefore, it is necessary to develop a new method for thalassemia detection with high sensitivity, low cost, and simple and rapid operation.…”