The updated beta-spectrin mutations in patients with hereditary spherocytosis by targeted next-generation sequencing

Fan, Jia; Yao, Lilan; Lu, Daru; Yao, Yanhua; Sun, Yajuan; Tian, Yafei; Li, Mou; Chen, Linbo; Zhao, Letian; Qiao, Shenglong; Hu, Shaoyan; Zhu, Yiwen

doi:10.1038/s10038-021-00946-6

Cited by 5 publications

(5 citation statements)

References 16 publications

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“…In general, spectrin deficiency is frequently identified as the causative factor in hereditary spherocytosis (OMIM, # 616649 and # 182900). Cases with autosomal recessive inheritance are caused by defects in α-spectrin, whereas dominant inheritance is associated with β-spectrin gene defects or secondary to ankyrin gene defects [9][10][11][12]. This different pattern of inheritance of hereditary spherocytosis for the SPTA1 and SPTB genes is a consequence of the differences in regulation of expression of these proteins.…”

Section: Introductionmentioning

confidence: 99%

Identification of a Novel Mutation of β-Spectrin in Hereditary Spherocytosis Using Whole Exome Sequencing

Bogusławska

Skulski

Machnicka

et al. 2021

IJMS

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Hereditary spherocytosis (HS), the most commonly inherited hemolytic anemia in northern Europeans, comprises a group of diseases whose heterogeneous genetic basis results in a variable clinical presentation. High-throughput genome sequencing methods have made a leading contribution to the recent progress in research on and diagnostics of inherited diseases and inspired us to apply whole exome sequencing (WES) to identify potential mutations in HS. The data presented here reveal a novel mutation probably responsible for HS in a single Polish family. Patients with clinical evidence of HS (clinical symptoms, hematological data, and EMA test) were enrolled in the study. The examination of the resulting WES data showed a number of polymorphisms in 71 genes associated with known erythrocyte pathologies (including membranopathies, enzymopathies, and hemoglobinopathies). Only a single SPTB gene variant indicated the possible molecular mechanism of the disease in the studied family. The new missense mutation p.C183Y was identified using WES in the SPTB gene, which is most likely the cause of clinical symptoms typical of hereditary spherocytosis (membranopathy) due to structural and functional impairments of human β-spectrin. This mutation allows for a better understanding of the molecular mechanism(s) of one of the membranopathies, hereditary spherocytosis.

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Section: Introductionmentioning

confidence: 99%

Identification of a Novel Mutation of β-Spectrin in Hereditary Spherocytosis Using Whole Exome Sequencing

Bogusławska

Skulski

Machnicka

et al. 2021

IJMS

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“…Previous studies have shown that mutations in this gene are associated with hereditary polycythemia [36] . SPTB, encoding another kind of spectrin protein, is related to hereditary spherocytosis [37] . VNN1 encodes the enzyme vascular non-in ammatory molecule-1 (vanin 1) and its major function is related to its pantetheinase activity [38] .…”

Section: Discussionmentioning

confidence: 99%

Secretory Phenotype in Peripheral Blood Mononuclear Cells of Elderly Patients with Rheumatoid Arthritis

Wang,

Chen,

Shen

et al. 2024

Rejuvenation Research

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The senescence-associated secretory phenotype (SASPs) might increase risk of age-related diseases and concomitant diseases in elderly rheumatoid arthritis (ERA) patients. This study aims to investigate the SASPs in peripheral blood mononuclear cells (PBMCs) for ERA patients. We performed RNA-seq of the PBMCs from 5 aged RA (RA_A) and 4 young RA (RA_Y) patients. By comparing the differentially expressed genes (DEGs) of RA_Y and RA_A using DESeq package, we identi ed the senescent secretory phenotype of ERA. The Gene Ontology (GO) functional enrichment, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and GSEA analysis were performed using clusterPro ler package. The signi cant protein-protein interaction (PPI) networks identi ed by Cytoscape. The proteomics data that investigate secretory phenotype of ERA was download from proteomics database. The overlapping SASPs at the intersection of proteomic and transcriptomic were then validated using real-time PCR (RT-PCR). The PBMCs of RA_A and RA_Y had heterogeneity transcriptomic feature. By comparing RA_A with RA_Y groups, 348 up-regulated and 363 down-regulated DEGs were identi ed. Gene functional enrichment indicated that up-regulated DEGs in RA_A, SASPs for ERA patients, enriched in PI3K-Akt signaling pathway, MAPK signaling pathway, toll-like receptor family, neutrophil degranulation and immune-related pathways and so on. GSEA analysis indicated, humoral immune response pathways were activated in RA_A. By performing RT-PCR, these ve SASPs, SPTA1, SPTB, VNN1, TNXB, KRT1, in PBMCs of RA patients were nally validated. Our study revealed the aging phenotypes in PBMCs of RA patients, and validated ve SASPs, which providing novel insights for targeting SASPs therapy.

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“…Patients with congenital bone marrow failure (BMF) syndromes (Fanconi anemia, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, and dyskeratosis congenita) were excluded clinically and by laboratory assays, including DNA analysis by targeted next-generation sequencing. 29 The detected genes are listed in Supplementary Table 1 . All patients enrolled in this study were diagnosed with acquired SAA or acquired very severe aplastic anemia (VSAA) based on the guidelines.…”

Section: Methodsmentioning

confidence: 99%

Association between haploidentical hematopoietic stem cell transplantation combined with an umbilical cord blood unit and graft-versus-host disease in pediatric patients with acquired severe aplastic anemia

Yao

Tian

et al. 2022

Therapeutic Advances in Hematology

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Background: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) based on granulocyte colony-stimulating factor plus anti-thymocyte regimens (‘Beijing Protocol’) provides a salvage treatment for patients of acquired severe aplastic anemia (SAA) in China. However, graft- versus-host disease (GVHD) is a major impediment of haplo-HSCT due to human leukocyte antigen disparity. Recently, haplo-HSCT combined with umbilical cord blood (UCB) (haplo-cord HSCT) is performed in clinical trials to potentially reduce the risk of severe GVHD. Nevertheless, studies comparing GVHD in pediatric patients receiving haplo and haplo-cord HSCT for SAA are limited. Objective: The objective of this study was to investigate the impact of UCB co-infusion on GVHD in pediatric patients receiving haplo-HSCT for SAA. Design: We conducted a retrospective study of 91 consecutive SAA children undergoing haploidentical transplantation based on the ‘Beijing Protocol’ with or without co-infusion of UCB in our center. Methods: All patients received uniform non-myeloablative conditioning and GVHD prophylaxis. We compared baseline characteristics and transplant outcomes between the haplo ( n = 35) and haplo-cord ( n = 56) recipients. Results: All 91 patients achieved hematopoietic recovery from haploidentical donors, with a higher incidence of peri-engraftment syndrome observed with the haplo-cord group as compared with the haplo group (75.0% versus 48.6%, p = 0.029). Notably, the haplo-cord group showed a lower incidence of II–IV acute GVHD (aGVHD) than the haplo group (16.1% versus 42.9%, p = 0.002). Observed incidences of chronic GVHD (cGVHD) and moderate to severe cGVHD in the haplo-cord group were also lower than that in the haplo group (25.6% versus 51.3%, p = 0.019; 16.2% versus 41.3%, p = 0.016, respectively). Haplo-cord HSCT was identified as the only factor associated with a lower incidence of II–IV aGVHD and cGVHD in multivariate analysis. However, no differences were observed between the two groups for infections and survival outcomes. Conclusion: Our data indicated that co-infusion of UCB in ‘Beijing Protocol’-based haplo-HSCT may be effective for reducing the risk of severe GVHD in SAA children.

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The updated beta-spectrin mutations in patients with hereditary spherocytosis by targeted next-generation sequencing

Cited by 5 publications

References 16 publications

Identification of a Novel Mutation of β-Spectrin in Hereditary Spherocytosis Using Whole Exome Sequencing

Identification of a Novel Mutation of β-Spectrin in Hereditary Spherocytosis Using Whole Exome Sequencing

Secretory Phenotype in Peripheral Blood Mononuclear Cells of Elderly Patients with Rheumatoid Arthritis

Association between haploidentical hematopoietic stem cell transplantation combined with an umbilical cord blood unit and graft-versus-host disease in pediatric patients with acquired severe aplastic anemia

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