Molecular Characterization of β- and α-Globin Gene Mutations in Individuals with Borderline Hb A<sub>2</sub> Levels

Satthakarn, Surada; Panyasai, Sitthichai; Pornprasert, Sakorn

doi:10.1080/03630269.2020.1826327

Cited by 10 publications

(14 citation statements)

References 23 publications

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“…60 Out of 17 studies, 47.1% (n=8) compared HbA2 levels between |3-thalassemia traits and |3-thalassemia traits co-inherited with α-thalassemia. 34 - 36 , 45 - 47 , 55 , 60 Although four studies (50%) observed a reduction in HbA2 level when a-thalassemia co-exists, 34 , 35 , 47 , 55 only two studies (25%) reported a possible effect of this on BTT diagnosis. 47 , 55 Of these two, one showed that HbA2<4.0% can occur when HbH disease (a-thalassemia intermedia) co-exists with the BTT.…”

Section: Resultsmentioning

confidence: 99%

“… 34 - 36 , 45 - 47 , 55 , 60 Although four studies (50%) observed a reduction in HbA2 level when a-thalassemia co-exists, 34 , 35 , 47 , 55 only two studies (25%) reported a possible effect of this on BTT diagnosis. 47 , 55 Of these two, one showed that HbA2<4.0% can occur when HbH disease (a-thalassemia intermedia) co-exists with the BTT. 55 Surprisingly, out of 17 studies, 47.1% (n=8) reported a marginal increase in HbA2 levels among a-thalassemia traits without β-thalassemia heterozygosis.…”

Section: Resultsmentioning

confidence: 99%

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Unresolved laboratory issues of the heterozygous state of β-thalassemia: a literature review

Thilakarathne,

Jayaweera,

Premawardhena

2023

haematol

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Although considered a mild clinical condition, many laboratory issues of the carrier state of beta-thalassaemia remain unresolved. Accurate laboratory screening of beta-thalassaemia traits is crucial for preventing the birth of a beta-thalassaemia major child. Identification of carriers in the laboratory is affected by factors that influence red cell indices and HbA2 quantification. Silent mutations and co-inheriting genetic and non-genetic factors affect red cell indices which decreases the effectiveness of the conventional approach. Similarly, the type of beta mutation, co-inheriting genetic and non-genetic factors, and technical aspects, including the analytical method used and variations in the HbA2 cutoff values, affect the HbA2 results leading to further confusion. However, the combination of MCV, MCH and haemoglobin analysis increases the diagnostic accuracy. Diagnostic problems arising from non-genetic factors can be eliminated by carefully screening the patient’s clinical history. Still, issues due to certain genetic factors, such as Krüppel-like factor 1 gene mutations and alpha triplication remain unresolved. Each laboratory should determine the populationspecific reference ranges and be wary of machine-related variations of HbA2 levels, the prevalence of silent mutations in the community.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Unresolved laboratory issues of the heterozygous state of β-thalassemia: a literature review

Thilakarathne,

Jayaweera,

Premawardhena

2023

haematol

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“…Hematological characteristics of β -thalassemia heterozygotes have wide variation based on the type of mutation [ 12 , 13 ]. Baliyan et al' [ 14 ] study in India showed that MCV <74 fL combined with MCH <28 pg can be used as a cutoff for the screening test of thalassemia in antenatal anemic woman in South Asian region, if the HPLC in the facility does not exist (sensitivity 95%, specificity 16%).…”

Section: Discussionmentioning

confidence: 99%

Hematological Parameters in Individuals with Beta Thalassemia Trait in South Sumatra, Indonesia

Sari

Wahidiyat

Setianingsih

et al. 2022

Anemia

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Background. β-Thalassemia has a very wide clinical variation, depending on the severity of the patient’s condition. Individuals with β-thalassemia traits are usually asymptomatic; however, laboratory examination will show mild anemia with microcytic hypochromic erythrocytes morphology with wide variation depending on the genotype. This study was conducted to determine the reference value of hematological parameters and hemoglobin (Hb) analysis based on the phenotype of β-thalassemia (β0 and β+) and determine the differences of hematological characteristics between the two phenotypes. Methods. This cross-sectional study was conducted by evaluating the hematological parameters and Hb analysis of the β-thalassemia trait in the family of thalassemia patient population. The subjects were divided into β0 and β+. The subject with normal Hb analysis with or without iron deficiency was excluded. Results. A total of 203 subjects with thalassemia traits were included from the families of thalassemia patients, consisting of 101 subjects with β0-thalassemia, 82 subjects with β+-thalassemia, and the mutation had not been found in 20 subjects. There was a relationship in the mean/median of hematological parameters, HbA2 and HbF, between β0-thalassemia and β+-thalassemia ( P < 0.05 ). ROC for each hematological parameter, HbA2 and HbF, showed that the highest diagnostic value based on the area under the curve was mean corpuscular hemoglobin (MCH) (0.900) and mean corpuscular volume (MCV) (0.898). The cutoff point of MCH for β0-thalassemia trait was ≤20.5 pg (sensitivity 85%, specificity 90%) and MCV was ≤66.8 fL (sensitivity 87%, specificity 87%). Conclusion. MCH values can be used as a screening tool for predicting β0-thalassemia in the relatives of thalassemia patients in the South Sumatra population.

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“…The β −50 allele is not part of the conventional thalassemia genetic analysis in China's official guidelines; there is only one commercial thalassemia genetic detection reagent produced by Yilifang Bio that includes this allele in the detection range; nevertheless, few institutions use this kit, and laboratories report very few of this allele. The hematological thalassemia phenotype of carriers first reported by Li et al was significant; however, the internal data shared among laboratories suggested that the hematological phenotype of individuals carrying this variant was not significant (Chen et al, 2020;Shang et, al., 2017;Satthakarn et al, 2020). Recently, Zhao et al reported two groups of families carrying the variant and stated that the variant is a silent β-thal allele (Zhao et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…The index family's hematological patterns changed significantly; therefore, the authors suggested that the variant was more like a β + thalassemia allele. In follow-up tests, various teams occasionally detected the variant, and they disagreed about the nature of the variant (Chen et al, 2020;Satthakarn et al, 2020). Zhao et al later suggested that the variant is a silent β-thal allele (Zhao et al, 2020).…”

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confidence: 99%

Identification of the β thalassemia allele β^–50 and analysis of the hematology data of carriers in a southern Chinese population

Long

Liu

2021

Annals of Human Genetics

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During a routine test, we identified a 38-year-old man who had a positive hematology screening result but was negative for hot spot variants of his thalassemia gene. Further analysis identified β -50 (HBB: c.-100G>A). It was first suggested that β -50 was a β + -thal allele, and some research groups suggested this allele was a silent β-thal allele. To fully understand the hematological phenotype of the β -50 allele, we screened for individuals carrying β -50 in the general population and performed hematology analysis on these carriers. A real-time PCR detection system was designed to verify samples carrying β -50 . Twenty-one thousand samples and 43 pedigree samples were screened, and 86 β -50 carriers were detected. We performed hematological analysis on 65 individuals older than 3 years who had normal serum ferritin and analyzed the data. A total of 34.62% of the β -50 /β N individuals had mean cellular volume (MCV) or mean cellular hemoglobin (MCH) values slightly lower than the positive cutoff value of screening; the β -50 carriers' Hb A 2 value was slightly elevated. According to the test results, β -50 carriers have slight changes in hematology parameters, including slight decreases in MCV and MCH and slight increases in Hb A 2 ; however, these effects do not reach the degree of traditional β + alleles. Females with genotype β -50 /β 0 show a degree of decline in hematological indicators during pregnancy. Therefore, we should describe β -50 as a β ++ thalassemia allele, and identification of β -50 can explain slight changes in hematological indicators in some carriers.

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Molecular Characterization of β- and α-Globin Gene Mutations in Individuals with Borderline Hb A₂ Levels

Cited by 10 publications

References 23 publications

Unresolved laboratory issues of the heterozygous state of β-thalassemia: a literature review

Unresolved laboratory issues of the heterozygous state of β-thalassemia: a literature review

Hematological Parameters in Individuals with Beta Thalassemia Trait in South Sumatra, Indonesia

Identification of the β thalassemia allele β^–50 and analysis of the hematology data of carriers in a southern Chinese population

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Molecular Characterization of β- and α-Globin Gene Mutations in Individuals with Borderline Hb A2 Levels

Cited by 10 publications

References 23 publications

Unresolved laboratory issues of the heterozygous state of β-thalassemia: a literature review

Unresolved laboratory issues of the heterozygous state of β-thalassemia: a literature review

Hematological Parameters in Individuals with Beta Thalassemia Trait in South Sumatra, Indonesia

Identification of the β thalassemia allele β–50 and analysis of the hematology data of carriers in a southern Chinese population

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Molecular Characterization of β- and α-Globin Gene Mutations in Individuals with Borderline Hb A₂ Levels

Identification of the β thalassemia allele β^–50 and analysis of the hematology data of carriers in a southern Chinese population