Thalassemias: from gene to therapy

G, De Simone; Quattrocchi, Alberto; Mancini, Benedetta; Masi, Alessandra di; Nervi, Clara; Ascenzi, Paolo

doi:10.1016/j.mam.2021.101028

Cited by 29 publications

(29 citation statements)

References 242 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that there were changes in the number, volume, and hemoglobin content of red blood cells in the Li population. Thalassemia is caused by Hb α or β autosomal recessive genetic diseases caused by reduced chain synthesis, and this is common in tropical countries [29]. In 1982, a survey report on thalassemia based on 100,000 people in Hainan Province showed that the incidence of HbH disease in the Li population was 0.233%, much higher than the 0.027% in the Han population [30].…”

Section: Some Ideas Regarding the Rbt Characteristics Of The Nationalitymentioning

confidence: 99%

Blood routine reference value range should be adjusted according to regional and ethnic characteristics

Guo

Liu

Zhang

et al. 2022

Preprint

View full text Add to dashboard Cite

Objective To further understand the influence of regional and ethnic factors on blood routine indicators and to provide reference for formulating the range of blood routine reference values for different regions and ethnic groups in China. Methods The routine blood test (RBT) results of 617 healthy men aged 18–45 years old of the Li, Tibet, and Han nationalities living in the city of Sanya, Hainan Province (200 m), the city of Xining, Qinghai Province (2300 m), and Maduo County of Qinghai Province (4300 m) for a long time were studied. Eight indexes, such as the red blood cell (RBC), hemoglobin (Hb) and platelet (PLT) counts, were compared and analyzed. Results With an increase in altitude, the RBT index values and change trends of the different ethnic groups were different. When the altitude increased by 2000 m, the RBC and Hb increased by 6.6% and 8.1%, respectively, and the PLT decreased by 16.8%. However, the RBC, Hb, and PLT of the Tibetan subjects decreased by 7.4%, 5.1%, and 3.0%, respectively. In the same region, there were also significant differences in the RBT index values among the ethnic groups. The RBC increased, Hb decreased, and PLT did not change in the Li nationality in Sanya compared with the Han nationality. The RBC, Hb, and PLT of Tibetans in the Xining area were significantly higher than those of the Han population. Referring to the current RBT reference value range in China, the abnormal rates of the various RBT index values of the enrolled population were high. By utilizing Hb as an example, 27.7% of the Li nationality in Sanya was low, 67.0% of the Tibetan nationality in Xining was high, and 89.4% of the Maduo Han nationality was high. The PLT was lower in the Sanya Li nationality (13.8%) and the Maduo Han nationality (88.3%). Conclusion Regional and ethnic factors have a significant impact on the RBT, and the current range of normal values of the RBT in China needs to be revised and adjusted.

show abstract

Section: Some Ideas Regarding the Rbt Characteristics Of The Nationalitymentioning

confidence: 99%

Blood routine reference value range should be adjusted according to regional and ethnic characteristics

Guo

Liu

Zhang

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…This β‐globin switching and expression are regulated by the interaction of promoters with the locus control region (LCR). LCR for β‐globin consists of hypersensitivity sites (HSs), that is, HS1, HS2, HS3, HS4, and HS5 at the 5′ end of the HbE gene and another HS1 is present downstream of the β‐globin gene cluster and is given the name 3′‐HS1 (De Simone et al, 2021).…”

Section: Potential Of Pe In β‐Thalassemiamentioning

confidence: 99%

Prime editing: A potential treatment option for β‐thalassemia

Arif

Farooq

Ahmad

et al. 2022

Cell Biology International

View full text Add to dashboard Cite

The potential to therapeutically alter the genome is one of the remarkable scientific developments in recent years. Genome editing technologies have provided an opportunity to precisely alter genomic sequence(s) in eukaryotic cells as a treatment option for various genetic disorders. These technologies allow the correction of harmful mutations in patients by precise nucleotide editing. Genome editing technologies such as CRISPR (clustered regularly interspaced short palindromic repeat) and base editors have greatly contributed to the practical applications of gene editing. However, these technologies have certain limitations, including imperfect editing, undesirable mutations, off‐target effects, and lack of potential to simultaneously edit multiple loci. Recently, prime editing (PE) has emerged as a new gene editing technology with the potential to overcome the above‐mentioned limitations. Interestingly, PE not only has higher specificity but also does not require double‐strand breaks. In addition, a minimum possibility of potential off‐target mutant sites makes PE a preferred choice for therapeutic gene editing. Furthermore, PE has the potential to introduce insertion and deletions of all 12 single‐base mutations at target sequences. Considering its potential, PE has been applied as a treatment option for genetic diseases including hemoglobinopathies. β‐Thalassemia, for example, one of the most significant blood disorders characterized by reduced levels of functional hemoglobin, could potentially be treated using PE. Therapeutic reactivation of the γ‐globin gene in adult β‐thalassemia patients through PE technology is considered a promising therapeutic strategy. The current review aims to briefly discuss the genome editing strategies and potential applications of PE for the treatment of β‐thalassemia. In addition, the review will also focus on challenges associated with the use of PE.

show abstract

“…According to the type of defective gene, thalassemias are divided into α-, β-, γ-, δ-, δβ-, and εγδβ-thalassemias. Among them, α-thalassemia (α-thal) and β-thalassemia (β-thal) were the two main types (Barnett, 2019;Shafique et al, 2021;De Simone et al, 2022). Carriers of thalassemia mutations account for about 5% of the global population, particularly in tropical and subtropical areas, for instance, North Africa, the Mediterranean region, India, Southeast Asia, Pakistan, and the Middle East (Merkeley and Bolster, 2020).…”

Section: Introductionmentioning

confidence: 99%

Prevalence and molecular characterization of alpha and beta-Thalassemia mutations among Hakka people in southern China

Zeng¹,

Liu²,

et al. 2022

Genet. Mol. Biol.

View full text Add to dashboard Cite

Our aim was to investigate molecular features of thalassemia for proper clinical consultation and prevention in Heyuan. In our research, a total of 25,437 positive screening subjects were further subjected to a genetic analysis of α-thalassemia (α-thal) and β-thalassemia (β-thal). The deletion of α-thal mutation was tested by Gap-PCR, while the non-deletion of α-thal and β-thal mutation were identified by the PCR-reverse dot blot (PCR-RDB) technique. Nested PCR detected Hkαα/--SEA and Hkαα/αα. Among the 25,437 positive screening subjects, 44.09% (11216/25437) subjects were bearers of thalassemia variations, and 30.85% (7847/25437) subjects showed α-thal changes alone. Among the 23 genotypes with α-thal mutation alone, the three common genotypes were --SEA /αα(68.34%), -α 3.7 /αα (16.44%), and -α 4.2 /αα(6.38%). Of the 11.50% (2924/25437) subjects and 29 genotypes with β-thal mutation alone, the three common genotypes were β CD41-42 /β N (36.22%), β IVS-II-654 /β N (30.88%), and β -28 /β N (13.47%). Additionally, of the 1.75% (445/25437) subjects and 55 genotypes showed both αand β-thal mutations. We also identified 269 cases of Hb H and six patients of Hkαα. Furthermore, the common genotypes of α-thal and β-thal mutations were consistent with allele frequencies of mutations. Our study establishes molecular features of thalassemia among Hakka people in Heyuan. It will be useful for developing strategies to prevent thalassemia.

show abstract

Thalassemias: from gene to therapy

Cited by 29 publications

References 242 publications

Blood routine reference value range should be adjusted according to regional and ethnic characteristics

Blood routine reference value range should be adjusted according to regional and ethnic characteristics

Prime editing: A potential treatment option for β‐thalassemia

Prevalence and molecular characterization of alpha and beta-Thalassemia mutations among Hakka people in southern China

Contact Info

Product

Resources

About