Insights in Thalassemia: From Genomics to Clinical Practice

Editorial

14 July 2023

Editorial: Insights in thalassemia: from genomics to clinical practice

Catherine Lynn T. Silao

Zarina Abdul Latiff

Petros Kountouris

and

Bin Alwi Zilfalil

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0 citations

Editors

Zarina Abdul Latiff

National University of Malaysia

Zilfalil Bin Alwi

University of Science Malaysia (USM)

Petros Kountouris

The Cyprus Institute of Neurology and Genetics

CATHERINE LYNN T. SILAO

College of Medicine, University of the Philippines Manila

Impact

Socio-demographic and clinical characteristics of 70 thalassemia patients.

Original Research

06 October 2022

Barriers to adherence to iron chelation therapy among adolescent with transfusion dependent thalassemia

Rafaa Mohamed

, 2 more and

Zarina Abdul Latiff

Study background: Thalassemia is the commonest genetic blood disorder in Malaysia which requires life-long blood transfusions. From a total of 7,984 thalassemia patients in Malaysia, adolescent age group account for the highest number of patients (2,680 patients, 33.57%). In developed countries, the average rate of adherence to long-term treatment among children and adolescents is only 58%. Sub-optimal adherence to iron chelation therapy may impact the outcome and quality of life in these patients. Thus, assessing adherence level and identification of risk factors for non-adherence is essential in optimizing management.

Objectives: To determine the association between mean serum ferritin level with self-reported level of adherence to iron chelation therapy in transfusion dependent thalassemia (TDT) adolescents in Hospital Tengku Ampuan Afzan (HTAA), Kuantan and Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Cheras; to determine the association between socio-demographic factors and patients’ knowledge on thalassemia and iron chelation therapy with the level of adherence.

Materials and methods: This was a cross-sectional study conducted between 1st March 2019 and 31st March 2020. Data was collected through face-to-face interview by a single interviewer during the thalassemia clinic follow up, with content validated questionnaires. The questionnaires comprised four sections which included socio-demographic data, medication adherence questionnaire, knowledge of disease, and clinical characteristics of the participants.

Results: A total of 70 participants were recruited. Results showed that only 51.4% of participants had good adherence to iron chelation therapy. There was a significant association between monthly household incomes of the family with the level of adherence to iron chelation (p-value 0.006). There was also an association between the mean serum ferritin levels with total Adherence Starts with Knowledge (ASK-12) score (p-value 0.001). However, there was no association between knowledge on thalassemia with the level of adherence.

Conclusion: Adherence to iron chelation was generally unsatisfactory amongst adolescents with TDT as only 51.4% had good adherence. Low monthly household income of the family may affect adherence to iron chelation therapy in TDT patients. As adherence remains to be an issue amongst adolescent thalassemia patients, management should include regular and objective assessments to address this problem so as to optimize patient outcome.

3,610 views

12 citations

$The general workflow for the screening and diagnosis of α- and β-thalassemia using traditional and NGS-based methods. Figure adapted from Chen et al. (28) and Nigam et al. (55). FBC, full blood count; HPLC, high-performance liquid chromatography; ARMS, amplification refractory multiple sequencing; PCR, polymerase chain reaction; MLPA, multiplex ligation-dependent probe amplification.$

Mini Review

29 September 2022

Applications of next generation sequencing in the screening and diagnosis of thalassemia: A mini-review

Syahirah Amnani Suhaimi

, 2 more and

Mas Rina Wati Abdul-Hamid

5,181 views

9 citations

The DASS 21 recommended cut-off points (7).

Original Research

22 August 2022

Psychological distress and coping strategies among the caretakers of children with transfusion-dependent thalassemia

Azizah Othman

, 2 more and

Norsarwany Mohamad

3,811 views

3 citations

Original Research

30 November 2022

Molecular and hematological studies in a cohort of beta zero South East Asia deletion (β°-thal SEA) from Malaysian perspective

Norafiza Mohd Yasin

, 7 more and

Mohamed Saleem

2,427 views

2 citations

Original Research

29 September 2022

Activated CD4 + T lymphocyte is a potential biomarker for acute graft-vs.-host disease after hematopoietic stem cell transplantation in children with transfusion-dependent β-thalassemia

Ken Huang

and

Jianming Luo

1,419 views

0 citations

Original Research

22 March 2023

An analysis of the distribution and spectrum of alpha thalassemia mutations in Rasht City, North of Iran

Mona Asghari Ahmadabad

, 7 more and

Bahram Darbandi

1,319 views

0 citations

Original Research

15 July 2022

Analysis of Common Beta-Thalassemia (β-Thalassemia) Mutations in East Java, Indonesia

Yetti Hernaningsih

, 7 more and

Narazah Mohd Yusoff

Background: The frequency of the beta-thalassemia (β-thalassemia) gene in Indonesia ranges from 3 to 10%. However, in the East Java province, there is still limited information on the prevalence of β-thalassemia mutations in clinically diagnosed beta-thalassemia patients of East Java. Therefore, this study aimed to characterize β-thalassemia mutations in selected patients in the East Java province of Indonesia.

Methods: This is an analytical observational study. Diagnosis of β-thalassemia was based on clinical presentation, complete blood count (CBC), and hemoglobin (Hb) electrophoresis. Blood specimens taken from each patient in three ethylenediaminetetraacetic acid (EDTA) tubes were analyzed for CBC and Hb electrophoresis and processed for DNA extraction and subsequent polymerase chain reaction (PCR). Detection of mutations in Hemoglobin Subunit Beta (HBB) gene exons 1–3 of the β-thalassemia gene as the common mutation in Indonesia was done using PCR followed by Sanger sequencing.

Results: In total, 33 (n = 33) participants were involved in this study with ages ranging from 5 to 17 years comprising 19 women and 14 men. Their ethnic origins were Javanese (n = 30) and Chinese (n = 3). CBC results showed that mean ± standard deviation (SD) for Hb, red blood cell (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW)-CV were 81.2 ± 7.0 g/L; 3.40 ± 0.39 × 10⁹/L; 71.05 ± 5.72 fL; 24.12 ± 2.45 pg; 33.91 ± 1.47 g/dl; 24.38 ± 6.02%, respectively. Hb electrophoresis revealed that 5 out of 33 participants had beta-thalassemia and 28 out of 33 participants had hemoglobinopathy (Hb) E/beta-thalassemia. Results of Sanger sequencing showed the following genotype variations in the samples: 12 (36.4%) with β^CD26/β^IVS−I−5; 6 (18.2%) with β^CD26/β^CD35; 3 (9.1%) with β^CD26/β^IVS−I−2; 2 (6.1%) with β^CD27/28/β^CD40; 2 (6.1%) with β^IVS−I−1/β^CAP+1; and β^CD26/β^IVS−I−1; β^IVS−I−5/β^CAP+1; β^IVS−I−5/β^CD35; β^CD26/β^CD37; β^CD26/β^CD15; β^CD26/β^CD40; and β^IVS−I−5/β^CD19 in 1 (3%) sample, respectively, and 1 (3%) had no abnormality detected in sequencing even though electrophoresis showed abnormality in the migration pattern. The β^CD26/β^IVS−I−5 mutation was found in samples that were noted to have Hb E/beta-thalassemia on Hb electrophoresis.

Conclusion: The underlying genetic variations are heterogeneous in thalassemia patients in East Java, where 12 variants were found. The most common variant was β^CD26/β^IVS−I−5, which all accounted for Hb E/beta-thalassemia on Hb electrophoresis. Furthermore, 28 out of 33 participants had hemoglobinopathy (Hb) E/beta-thalassemia.

4,505 views

5 citations

Distribution of serum mean ferritin in H63D wild-type allele (CC) and H63D variant allele (CG) groups.

Original Research

12 July 2022

Frequency of Hereditary Hemochromatosis Gene (HFE) Variants in Sri Lankan Transfusion-Dependent Beta-Thalassemia Patients and Their Association With the Serum Ferritin Level

Padmapani Padeniya

, 3 more and

Vajira Dissanayake

2,653 views

2 citations

Review

15 June 2022

Genetic Manipulation Strategies for β-Thalassemia: A Review

Nur Atikah Zakaria

, 5 more and

Muhammad Farid Johan

Thalassemias are monogenic hematologic diseases that are classified as α- or β-thalassemia according to its quantitative abnormalities of adult α- or β-globin chains. β-thalassemia has widely spread throughout the world especially in Mediterranean countries, the Middle East, Central Asia, India, Southern China, and the Far East as well as countries along the north coast of Africa and in South America. The one and the only cure for β-thalassemia is allogenic hematopoietic stem cell transplantations (HSCT). Nevertheless, the difficulty to find matched donors has hindered the availability of this therapeutic option. Therefore, this present review explored the alternatives for β-thalassemia treatment such as RNA manipulation therapy, splice-switching, genome editing and generation of corrected induced pluripotent stem cells (iPSCs). Manipulation of β-globin RNA is mediated by antisense oligonucleotides (ASOs) or splice-switching oligonucleotides (SSOs), which redirect pre-mRNA splicing to significantly restore correct β-globin pre-mRNA splicing and gene product in cultured erythropoietic cells. Zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) are designer proteins that can alter the genome precisely by creating specific DNA double-strand breaks. The treatment of β-thalassemia patient-derived iPSCs with TALENs have been found to correct the β-globin gene mutations, implying that TALENs could be used as a therapy option for β-thalassemia. Additionally, CRISPR technologies using Cas9 have been used to fix mutations in the β-globin gene in cultured cells as well as induction of hereditary persistence of fetal hemoglobin (HPFH), and α-globin gene deletions have proposed a possible therapeutic option for β-thalassemia. Overall, the accumulated research evidence demonstrated the potential of ASOs-mediated aberrant splicing correction of β-thalassemia mutations and the advancements of genome therapy approaches using ZFNs, TALENs, and CRISPR/Cas9 that provided insights in finding the permanent cure of β-thalassemia.

9,826 views

8 citations

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