Development of molecular diagnostic platform for α0‐thalassemia 44.6 kb (Chiang Rai, ‐‐CR) deletion in individuals with microcytic red blood cells across Thailand

Introduction The α0‐thalassemia 44.6 kb or Chiang Rai (‐‐CR) deletion has been reported in northern Thailand and is capable of causing hemoglobin (Hb) H disease and a lethal α‐thalassemia genotype, Hb Bart's hydrops fetalis, in this region. However, there are no current data regarding the frequ...

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Published in:Annals of human genetics 2023-05, Vol.87 (3), p.137-145
Main Authors: Khamphikham, Pinyaphat, Hanmanoviriya, Oravee, Wongpalee, Somsakul Pop, Munkongdee, Thongperm, Paiboonsukwong, Kittiphong, Jopang, Yupin, Wangchauy, Chaowanee, Sancharernsook, Charan, Jinorose, Nathawat, Pornprasert, Sakorn
Format: Article
Language:English
Subjects:
Actin
Bart's hydrops fetalis
Blood diseases
Chiang Rai deletion
Control programs
Edema
Erythrocytes
Genotypes
Genotyping
Hemoglobin
Hydrops fetalis
microcytic anemia
severe thalassemia
Thalassemia
α‐thalassemia
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Summary:Introduction The α0‐thalassemia 44.6 kb or Chiang Rai (‐‐CR) deletion has been reported in northern Thailand and is capable of causing hemoglobin (Hb) H disease and a lethal α‐thalassemia genotype, Hb Bart's hydrops fetalis, in this region. However, there are no current data regarding the frequency of ‐‐CR nationwide due to a lack of effective diagnostic assay. Therefore, this study aimed to develop a reliable platform for simultaneous genotyping of ‐‐CR and two common α0‐thalassemias in Thailand (‐‐SEA and ‐‐THAI) and investigate the frequency of ‐‐CR across Thailand. Methods Multiplex gap‐PCR assay and five renewable plasmid DNA controls for ‐‐CR, ‐‐SEA, ‐‐THAI, α2‐globin (HBA2), and β‐actin (ACTB) were newly developed and validated with reference methods. The developed assay was further tested on 1046 unrelated individuals with a reduced mean corpuscular volume (MCV) of less than 75 fl for investigating genotypic and allelic spectrum of ‐‐CR. Results Our developed assay showed 100% concordance with reference methods. The results were valid and reproducible throughout hundreds of reactions. Comparison of the genotypic and allelic spectra revealed that heterozygous ‐‐SEA (‐‐SEA/αα) and ‐‐SEA alleles were dominant with the frequency of 22.85% (239/1046) and 13.34% (279/2092), respectively. Of these, ‐‐THAI and ‐‐CR were relatively rare in this population and comparable to each other with the allelic frequency of 0.14% (3/2092). Conclusion This study successfully established a reliable molecular diagnostic platform for genotyping of ‐‐CR, ‐‐SEA, and ‐‐THAI in a single reaction. Additionally, we demonstrated the frequency of ‐‐CR in Thailand for the first time and provided knowledge basis for the planning of severe α‐thalassemia prevention and control programs in Thailand, where thalassemia is endemic.
ISSN:0003-4800
1469-1809
DOI:10.1111/ahg.12496