bims-conane 2025-07-13 papers

Nucleic Acids Res. 2025 Jul 08. pii: gkaf637. [Epub ahead of print]53(13):

Dissecting the epigenetic regulation of the fetal hemoglobin genes to unravel a novel therapeutic approach for β-hemoglobinopathies.

Simone Amistadi, Letizia Fontana, Chiara Magnoni, Tristan Felix, Matteo Kane Charvin, Pierre Martinucci, Candice Gautier, Lilian Greau, Bettina Bessières, Panagiotis Antoniou, Oriana Romano, Eric Allemand, Claudio Mussolino, Annarita Miccio.

Beta-hemoglobinopathies are severe genetic diseases caused by mutations affecting the production of the adult β-globin chain. The clinical severity is mitigated by the co-inheritance of mutations that reactivate the production of the fetal β-like γ-globin in adults. However, the epigenetic mechanisms underlying the adult-to-fetal hemoglobin (HbA-to-HbF) switching are still not fully understood. Here, we used epigenome editing technologies to dissect the molecular mechanisms underlying γ- and β-globin gene regulation and to develop novel potential therapeutics for β-hemoglobinopathies. Targeted removal of DNA methylation by dCas9-Tet1 (alone or together with the deposition of histone acetylation by CBP-dCas9) at the fetal promoters led to efficient and durable γ-globin reactivation, demonstrating that DNA methylation is a driver for HbF repression. This strategy, characterized by high specificity and a good safety profile, led to a substantial correction of the pathological phenotype in erythroid cells from patients with sickle cell disease.

DOI: https://doi.org/10.1093/nar/gkaf637

Curr Opin Hematol. 2025 Jul 07.

Advances on the genetic basis of red cell membrane disorders.

Mary Risinger, Wenying Zhang, Theodosia A Kalfa.

PURPOSE OF REVIEW: The development and widespread use of genetic testing for diagnosis of red blood cell (RBC) membrane disorders and other hereditary hemolytic anemias (HHA) have expanded our understanding of these diseases and revealed additional complexities. We describe here such complexities and make suggestions regarding genotypic/phenotypic evaluation with the goal of early diagnosis of patients with HHA before inappropriate treatment or complications occur.
RECENT FINDINGS: Widespread use of clinical genetic diagnosis in patients, for more than a decade now, has revealed the heterogeneity of RBC membranopathies, even when caused by different variants in the same gene, and sometimes due to the same genetic variant, likely because of genetic modifiers or mutations in other genes encoding for RBC membrane proteins, enzymes, or globins. Many under-recognized diseases are now more easily diagnosed.
SUMMARY: Despite complexities in the genetic evaluation of RBC membranopathies, the future holds great promise for timely and accurate diagnosis. Correlation and documentation of genotypic and phenotypic data from affected individuals and family members will allow for improved detection and interpretation of genetic results. The use of such testing in newborns and children with HHA can optimize treatment decisions and explore possibilities for novel targeted or genetic therapies.

Keywords: hereditary hemolytic anemias; membranopathies; next-generation sequencing; red cell membrane disorders

DOI: https://doi.org/10.1097/MOH.0000000000000883

Mediterr J Hematol Infect Dis. 2025 ;17(1): e2025047

Elevated Endogenous Alveolar Carbon Monoxide Concentration in Patients with Transfusion-Dependent Thalassemia and Its Relation with Ineffective Erythropoiesis.

Yanni Xie, Guiping Liao, Hongyuan Zhang, Yali Zhou, Yunshuo Xiao, Tianhong Zhou, Dongmei Liu, Beibei Yang, Manlv Wei, Qiuying Wei, Changqing Wei, Lina Lu, Weiren Wang, Jian Huang, Zhili Geng, Hui Wu, Jingting Luo, Xiaolin Yin.

Keywords: Carbon monoxide; Ineffective erythropoiesis; Soluble transferrin receptor; Thalassemia

DOI: https://doi.org/10.4084/MJHID.2025.047

Clin Exp Med. 2025 Jul 10. 25(1): 242

Ropeginterferon alfa-2b as a promising alternative to conventional interferon in CDA type 1: a case report of two siblings.

Tyng-Wei Yang, Xavier Cheng-Hong Tsai, Yu-Hsuan Fu, Liang-In Lin, Hsin-An Hou.

Congenital dyserythropoietic anemia type I (CDA-I) is a rare hereditary anemia caused by CDAN1 or C15orf41 mutations, with CDAN1-related cases responding to interferon-alpha (IFN-α) therapy. However, traditional IFN-α requires frequent injections and often causes flu-like symptoms, which can hinder long-term adherence. Here, we present the first documented use of ropeginterferon alfa-2b, a next-generation pegylated interferon, in two patients with CDA-I. Both patients, who were previously transfusion dependent, achieved transfusion independence and improved hemoglobin levels after transitioning from recombinant IFN-α to ropeginterferon alfa-2b with biweekly dosing. This treatment preserved efficacy while minimizing adverse effects and the injection burden. Our findings suggest that ropeginterferon alfa-2b may serve as a more tolerable and effective long-term treatment. Further prospective large-scale studies are needed to validate its broader clinical applicability.

Keywords: CDA; CDAN1; Ropeginterferon alfa-2b

DOI: https://doi.org/10.1007/s10238-025-01785-x

Sultan Qaboos Univ Med J. 2025 May 02. 25(1): 141-145

Severe Haemolysis in Patients with Glucose-6-Phosphate Dehydrogenase Deficiency Secondary to Dengue Fever: Analysis of 3 cases from Oman.

Antara Gokhale, Huda Al Khalili, Mahmoud Al Abri.

Dengue fever (DF) is a viral fever transmitted by the Aedes species of mosquitoes. Globalisation has led to worldwide spread of DF including Oman. High incidence of glucose-6-phosphate dehydrogenase (G6PD) deficiency is present in Oman's population but is often undiagnosed. We report 3 G6PD-deficient patients admitted in a tertiary care hospital in Muscat, Oman in 2023 with DF that later triggered haemolysis. It proved fatal in 1 case and caused irreversible renal damage requiring dialysis in the other case. Both DF and G6PD deficiency can cause bleeding. Both need supportive treatment. G6PD deficiency with concomitant viral infections have been reported to increase morbidity and mortality. Haemolysis triggered due to DF in G6PD deficient patients has not been reported in the literature. If the clinical course or haemolytic pattern in DF patients deviates from what is to be expected, an associated haemolytic disorder should be considered especially in regions with high prevalence.

Keywords: Case Report; Dengue Fever; Glucose-6-Dehydrogenase Deficiency; Hemolysis; Oman; Organ Dysfunction

DOI: https://doi.org/10.18295/squmj.10.2024.059