Genotype-Phenotype Correlation of β-Thalassemia in Malaysian Population: Toward Effective Genetic Counseling

Abdullah, Uday Younis Hussein; Ibrahim, Hishamshah Mohd; Mahmud, Noraesah; Salleh, Mohd Zaki; Kek, Teh Lay; Noorizhab, Mohd Nur Fakhruzzaman; Zilfalil, Bin Alwi; Jassim, Haitham Muhammed; Wilairat, Prapin; Fucharoen, Suthat

doi:10.1080/03630269.2020.1781652

Cited by 9 publications

(8 citation statements)

References 23 publications

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“…Of 37 studies regarding factors affecting RBC indices, 67.6% (n=25) identified silent or mild β-thalassemia carriers with normal or marginal MCV and/or MCH. Of 25 studies, 6 (24%) originated from Italy, 6 , 22-26 5 (20%) from India, 14 , 27-30 4 (16%) from China, 31-34 2 (8%) each from Thailand, 35 , 36 Iran 37 , 38 and Pakistan, 39 , 40 one (4%) each from Turkey, 41 Bahrain, 42 Malaysia, 43 and Spain. 44 Silent or mild β-thalassemia mutations reported from different countries are listed in Table 1 .…”

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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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%

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

Thilakarathne,

Jayaweera,

Premawardhena

2023

haematol

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“…Although this study recruited patients from several provinces of southern Thailand, a similar pattern of the most common β-thalassemia mutations was observed. The origin of patients may explain the difference in distribution; for example, codons 41/42 (-TTCT) are very common in individuals of Chinese origin ( 45 , 46 ), whereas IVS I-5 (G>C) is very common in the Malay ( 49 ) and Asian Indian ( 50 ) populations. Interestingly, the present study demonstrated comparable frequencies of codons 41/42; -TTCT (23.9%) and IVS I-5; G>C (23.4%) because of the higher sample size of Thai-Muslim patients.…”

Section: Discussionmentioning

confidence: 99%

Genetic predictions of life expectancy in southern Thai patients with β0‑thalassemia/Hb E

et al. 2022

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The types of β-thalassemia mutations, α-thalassemia interactions, and Hb F-associated SNPs have been described in association with variable disease phenotypes. This study aimed to determine the updated spectrum of β-thalassemia mutations and evaluate the contribution of primary and secondary genetic modifiers and SNPs to disease severity, age at onset, and predicted life expectancy in southern Thai β-thalassemia patients. A total of 181 β-thalassemia patients were enrolled and 135 β 0 -thalassemia/Hb E patients without α-thalassemia interactions were divided into three categories according to disease severity, age at onset, and predicted life expectancy. A total of 16 β-thalassemia mutations were identified in this study, and the three most common β-thalassemia mutations accounted for 61.4% of all mutations. It was also found that the Xmn I polymorphism and rs2071348 were associated with age at onset and the predicted life expectancy. More than 82% of β 0 -thalassemia/Hb E patients with CC genotype ( Xmn I) were 3 years old or younger at onset. Additionally, >90% of the higher predicted life expectancy in β 0 -thalassemia/Hb E patients had the T allele of Xmn I. Therefore, genetic prediction for age at onset and life expectancy is beneficial and practical during prenatal diagnosis or newborn screening for better genetic counseling and optimal management.

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“…Hemoglobin A (HbA) is the most dominant type of hemoglobin found in healthy adults and is made up of two α-and two β-globin chains (50,51). The normal synthesis of β-globin chains was found to be reduced in HbE/β-thalassemia patients (2,52).…”

Section: Discussionmentioning

confidence: 99%

Reduced hepcidin expression enhances iron overload in patients with HbE/β‑thalassemia: Α comparative cross‑sectional study

et al. 2021

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Iron homeostasis is regulated by hepcidin (HEPC) that controls the dietary iron absorption and iron recycling. HEPC deficiency contributes to iron overload in β-thalassemia patients. The present study aimed to investigate the correlation between HEPC concentration and serum iron status among hemoglobin E (HbE)/β-thalassemia patients and their parents (HbE trait and β-thalassemia trait) compared with healthy controls. This study is a comparative cross-sectional study in which iron profile and HEPC level were examined in 65 HbE/β-thalassemia patients (pretransfusion) and 65 parents at the Hospital Sultanah Nur Zahirah and in 130 students as healthy controls from Univesiti Sultan Zainal Abidin, Terengganu, Malaysia. Furthermore, six samples from each group (HbE/β-thalassemia patients, parents and healthy controls) were randomly selected for gene expression analysis of HEPC and ferroportin1 (FPN1) using reverse transcription quantitative PCR. The results demonstrated that serum HEPC level were significantly decreased in HbE/β-thalassemia patients and their parents (P<0.001) compared with healthy controls. In addition, the gene expression analysis showed a dramatically downregulated HEPC in HbE/β-thalassemia patients and their parents (P= 0.001) compared with healthy controls. However, there was a marked upregulation of FPN1 in HbE/β-thalassemia patients and their parents (P=0.001) compared with healthy controls. Iron profiling results revealed a significantly increased serum ferritin in HbE/β-thalassemia patients and their parents compared with healthy controls (P<0.001). In summary, the present study demonstrated that HEPC expression level and serum level were significantly decreased in HbE/β-thalassemia patients and their parents, which was combined with a marked increased FPN1 expression level and serum ferritin level compared with healthy volunteers. These findings supported the hypothesis that downregulated HEPC could lose its function as a negative regulator of FPN1, resulting in iron overload in HbE/β-thalassemia patients. Subsequently, assessing HEPC and FPN1 gene expression may be a useful tool to determine the risk of iron toxicity in patients with HbE/β-thalassemia and their parents, and could therefore be considered as a therapeutic target in the management of iron burden in these patients.

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Genotype-Phenotype Correlation of β-Thalassemia in Malaysian Population: Toward Effective Genetic Counseling

Cited by 9 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

Genetic predictions of life expectancy in southern Thai patients with β0‑thalassemia/Hb E

Reduced hepcidin expression enhances iron overload in patients with HbE/β‑thalassemia: Α comparative cross‑sectional study

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