bims-conane 2026-02-15 papers

Int J Mol Sci. 2026 Jan 25. pii: 1203. [Epub ahead of print]27(3):

miRNA-Mediated Regulation of γ-Globin to β-Globin Switching: Therapeutic Potential in β-Hemoglobinopathies.

Daniah Alotaibi, Falak Aldagdog, Sajidah Alramadhan, Basmah Almuhaidib, Nada Asiri, Leena Almodhi, Manar Alshabaan, Razan Alborhan, Chittibabu Vatte, Shamim Shaikh Mohiuddin, Amein K Alali, Alawi Habara.

Erythropoiesis is a tightly regulated developmental process that requires the switch from fetal hemoglobin (HbF) to adult hemoglobin (HbA). In β-hemoglobinpathies such as SCD and β-thalassemia, disease severity is influenced by the fetal-to-adult hemoglobin switch because persistence or induction of HbF will ameliorate the clinical manifestations. miRNAs play an essential role in regulating this switch by modulating the expression levels of key transcription factors, such as BCL11A, KLF1, and MYB, which repress γ-globin expression. Multiple miRNAs have been identified as potential modulators of the hemoglobin switch, including miR-144, miR-486, miR-26b, and miR-15a. The molecular interactions between miRNA and γ-to β-globin switch have the potential for new therapeutic interventions that aim to reactivate HbF expression to ameliorate β-hemoglobinopathies such as SCD and β-thalassemia. In this review, the latest advancements in miRNA-mediated regulation of Hb switching and nanoparticle-based strategies for miRNA delivery are explored.

Keywords: hemoglobin switch regulation; miRNA; nanoparticles; sickle cell disease; β-globin gene cluster regulation; β-thalassemia

DOI: https://doi.org/10.3390/ijms27031203

Front Genet. 2026 ;17 1659838

Case Report: Clinical and genetic analysis of a family with hereditary spherocytosis combined with familial chylomicronemia syndrome.

Yumei Qin, Yanping Liu, Kecheng Li, Yaoming Deng, Hualian Li, Xiao Chen, Xuan Pan, Xiaojing Huang, Mengyue Xie, Xingjiang Long, Shifu Tang.

Objective: This study was conducted to investigate the clinical and genetic characteristics of a family affected by hereditary spherocytosis (HS) combined with familial chylomicronemia syndrome (FCS), identify the pathogenic cause, and provide a basis for the clinical diagnosis, treatment, and genetic counseling of affected children.
Methods: Clinical data were collected from family members. High-throughput sequencing was performed to identify pathogenic variants in genes associated with HS and FCS in the proband. Suspected pathogenic mutations were confirmed in family members via PCR-Sanger sequencing. Bioinformatics analysis and three-dimensional protein structure prediction were also conducted.
Results: The proband presented with severe anemia, splenomegaly, and jaundice. Genetic testing revealed a heterozygous mutation, c.6005G>A (p.Trp2002*), in the spectrin beta chain (SPTB)gene (NM_001355436.2) and a missense mutation, c.292G>A (p.Ala98Thr), in the lipoprotein lipase (LPL) gene (NM_000237.3). The SPTB c.6005G>A (p.Trp2002*) mutation was inherited from the mother, who exhibited mild anemia, jaundice, and splenomegaly. The LPL c.292G>A (p.Ala98Thr) mutation was inherited from the father, who had hypertriglyceridemia. The SPTB c.6005G>A (p.Trp2002*) mutation is extremely rare in the general population.
Conclusion: The heterozygous mutations SPTB c.6005G>A (p.Trp2002*) and LPL c.292G>A (p.Ala98Thr) are the pathogenic causes in this family and provide a basis for clinical management and genetic counseling. Based on the HGMD, 1000G, and ExAC databases, the SPTB c.6005G>A (p.Trp2002*) mutation is reported here for the first time, enriching the mutation spectrum of the SPTB gene.

Keywords: LPL gene; SPTB gene; familial chylomicronemia syndrome; hereditary spherocytosis; novel mutation

DOI: https://doi.org/10.3389/fgene.2026.1659838

Arch Med Sci. 2025 ;21(6): 2671-2679

Comprehensive expression of long non-coding RNAs and association with iron and erythropoiesis regulatory proteins in transfusion-dependent β-thalassemia.

Ola M Al-Sanabra, Wafa' J Haza, Abeer A Haza'a, Diya Hasan, Mutaz Jamal Al-Khreisat, Majd M Alsaleh, Ahmad K Al Tibi.

Introduction: β-thalassemia is a genetic disorder characterized by a quantitative defect in β-globin synthesis caused by genetic and epigenetic alterations. However, the expression patterns of long non-coding RNAs (LncRNAs) and their relationship with genes and proteins involved in iron metabolism and erythropoiesis remain largely unknown. We aimed to investigate the expression of LncRNAs and their correlation with iron and erythropoiesis regulatory proteins in patients with transfusion-dependent β-thalassemia (TDβ-T).
Material and methods: Whole blood samples and clinical records were collected from 60 patients with TDβ-T and 20 healthy controls. Expression levels of selected LncRNAs were measured using qRT-PCR. Iron metabolism and erythropoiesis-related proteins were quantified using ELISA.
Results: TDβ-T patients exhibited significantly elevated levels of iron and erythropoiesis regulatory proteins, as well as increased expression of HAMP, GDF-15, FAM132B, and SLC40A1 compared to controls. Additionally, LncRNAs ANRIL, H19, LINCO133, MIAT, and NEAT1 were markedly upregulated, while LncRNA GAS5 was downregulated in patients with TDβ-T. Among these, LncRNAs NEAT1 and GAS5 showed the strongest diagnostic performance. A significant correlation was observed between the expression of HAMP and FAM132B and LncRNAs ANRIL, H19, LINCO133, and MIAT. Furthermore, LncRNA NEAT1 expression correlated positively with SLC40A1 and negatively with urea levels, whereas LncRNA GAS5 was inversely correlated with HAMP expression.
Conclusions: This study is the first to demonstrate altered LncRNA expression patterns and their associations with iron metabolism, erythropoiesis regulatory proteins, and urea levels in patients with TDβ-T. These findings provide new insights for future research and potential therapeutic targets.

Keywords: LncRNA GAS5; LncRNA NEAT1; iron regulatory proteins erythropoiesis regulatory proteins; transfusion-dependent β-thalassemia

DOI: https://doi.org/10.5114/aoms/205790

Hemasphere. 2026 Jan;10(1): e70280

Additive effect of multiple genetic variants in SEC23B and PIEZO1 on iron metabolism dyshomeostasis in hereditary anemias.

Hereditary anemias encompass a genetically heterogeneous spectrum of disorders, often involving multi-locus inheritance, which can complicate clinical management and worsen disease severity. This study investigates the impact of the co-inheritance of SEC23B loss-of-function pathogenic variants, which lead to congenital dyserythropoietic anemia type II (CDA II), and PIEZO1 gain-of-function pathogenic variants, associated with dehydrated hereditary stomatocytosis type I (DHS1), on hematological parameters and iron metabolism. Among 583 patients with suspected hereditary anemia, 13 were found to carry both SEC23B and PIEZO1 variants, leading to a dual diagnosis of CDA II and DHS1. Compared to those with isolated CDA II, these patients exhibited a significantly higher absolute reticulocyte count and bone marrow responsiveness index, alongside an increased prevalence of elevated ferritin levels. Functional studies in Hep3B human hepatoma cells confirmed that SEC23B knockdown combined with PIEZO1 gain-of-function led to marked ferritin accumulation and reduced hepcidin expression, driven by altered BMP/SMAD signaling and ERK1/2 MAPK pathway. These findings demonstrate how multi-locus inheritance can modify disease severity, particularly by exacerbating iron overload. Our results underscore the clinical relevance of comprehensive genetic testing for enhanced risk stratification and personalized management of hereditary anemias.

DOI: https://doi.org/10.1002/hem3.70280