Identification of new mutations in patients with hereditary spherocytosis by next-generation sequencing

Li, Qin; Nie, Yanbo; Zhang, Hong; Chen, Long; Zhang, Donglei; Lin, Yani; Ru, Kun

doi:10.1038/s10038-020-0724-z

Cited by 37 publications

(42 citation statements)

References 24 publications

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“…NGS has promoted molecular HS diagnosis, including both targeted panel and WES ( Roy et al, 2016 ; Russo et al, 2018 ; Xue et al, 2019 ; Qin L. et al, 2020 ). Here, the causal variants could be found in 100% of the cases using targeted NGS.…”

Section: Discussionmentioning

confidence: 99%

“…Most ANK1 and SPTB variants were indel (5/12) and non-sense (7/10), respectively. In the studies reported by Qin L et al and Wang R et al, which included 35 Chinese patients from Tianjin of China and 38 patients from Beijing China, respectively, it was shown that ANK1 and SPTB genes were the most frequently mutated genes ( Wang R. et al, 2018 ; Qin L. et al, 2020 ). Qin L et al found that six out of eight families showed a de novo variant, while we found that six out of thirteen families showed a lower rate of carrying de novo variants.…”

Section: Discussionmentioning

confidence: 99%

“…Application of next-generation sequencing (NGS) has led to impressive progress in genetic disorder diagnostics, and it has provided unprecedented benefits for both personalized laboratory medicine and patients with rare genetic disorders ( Di Resta and Ferrari, 2018 ; Prodan Zitnik et al, 2018 ). NGS has promoted HS molecular diagnosis compared to clinical practice, including both targeted panel and whole exome sequencing (WES) ( Xue et al, 2019 ; Qin L. et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Genetic and clinical features of Chinese HS cases have been frequently identified. Systematic investigation of the genotype-phenotype correlation in Chinese HS patients has been seldom reported ( Qin L. et al, 2020 ). Here, we systematically studied the genetic and clinical characteristics of patients with HS in Hubei province, China, and we investigated the genotype-phenotype correlation in those patients.…”

Section: Introductionmentioning

confidence: 99%

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Genetic and Clinical Characteristics of Patients With Hereditary Spherocytosis in Hubei Province of China

et al. 2020

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Hereditary spherocytosis (HS) is an inherited disorder characterized by anemia, splenomegaly, and spherical-shaped erythrocytes, caused by mutations in erythrocyte membrane Protein Genes ( ANK1 , SPTB , SLC4A1 , SPTA1 , and EPB42 ). We investigated molecular spectrum and genotype-phenotype correlation in HS patients in Hubei province, central China. Twenty-three patients with HS were included. A next-generation sequencing (NGS) panel targeting ANK1 , SPTB , SLC4A1 , SPTA1 , and EPB42 genes was used to screen potential variants. Sanger sequencing was applied to validate variants. Of the twenty-three patients, thirteen patients carried ANK1 variants, and ten patients harbored SPTB variants, including ten non-sense, six indel, four splice site, one start-loss, and one missense variant. Four out of twenty-two variants in our study were known, and eighteen variants were novel. Most ANK1 and SPTB variants were indel (5/12) or non-sense (7/10), respectively. Family member analysis in thirteen families showed that six variants were de novo . Variable expressivities were observed in a pair of twins with ANK1 c.341C > T variant, and two unrelated patients both carried ANK1 c.2T > A variant. Genotype-phenotype analysis found no significant difference between ANK1 and SPTB regarding the levels of Hb, RBC, MCV, MCH, and MCHC. However, variants in the ANK1 death domain were associated with lower levels of MCV and MCH compared to other ANK1 domains. In conclusion, NGS is a fast way to provide a molecular HS diagnosis. We also identified unique genetic and clinical characteristics of patients with HS in Hubei Province, China. However, a large sample size is needed to further investigate the genotype-phenotype correlation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genetic and Clinical Characteristics of Patients With Hereditary Spherocytosis in Hubei Province of China

et al. 2020

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“…EPB42, erythrocyte membrane protein band 4.2, was an ATP-binding protein which may regulate the correlation of protein 3 with ankyrin. It was reported that EPB42 could manipulate the shape and mechanical property of erythrocyte and have a high association with hereditary spherocytosis [40,41]. SLC4A1, the protein encoded by this gene was part of the anion exchanger family and was expressed in the erythrocyte plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Research of Key Modules and Hub Genes Associated with Primary Myelofibrosis by Weighted Co-expression Network Analysis.

Li¹,

Yuan²,

Zhang³

et al. 2020

Preprint

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Background: This study aimed to identify novel targets of diagnosis, therapy as well as prognosis for primary myelofibrosis (PMF).Methods: The gene expression profiles of GSE26049 was obtained from GEO dataset, weighted gene co-expression network analysis (WGCNA) was then performed to identify the most related modules with PMF. Subsequently, GO (Gene Ontology), KEGG (Kyoto Encyclopedia Genes and Genomes), GSEA (Gene Set Enrichment Analysis) and PPI (Protein-Protein Interaction) network were conducted to fully understand the detailed information of the green module.Results: Green module was strongly correlated with PMF disease after WGCNA analysis. 20 genes in green module were identified as hub genes responsible for the progression of PMF. Functional annotation and pathway analysis revealed that these hub genes were primarily enriched in erythrocyte differentiation, transcription factor binding, hemoglobin complex, transcription factor complex and cell cycle et al. Of which, EPB42, CALR, SLC4A1 and MPL had the most correlations with PMF.Conclusions: This study elucidated that genes EPB42, CALR, SLC4A1 and MPL were significantly more highly expressed in PMF samples than in normal samples. These four genes may be considered candidate prognostic biomarkers and potential therapeutic targets for early stage of PMF. Meanwhile, EPB42 and SLC4A1 were firstly found to be highly correlated with the progression of PMF.

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Sorting of cargo in the tubular endosomal network

Solinger

Spang

2022

BioEssays

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Intercellular communication is an essential process in all multicellular organisms. During this process, molecules secreted by one cell will bind to a receptor on the cognate cell leading to the subsequent uptake of the receptor-ligand complex. Once inside, the cell then determines the fate of the receptor-ligand complex and any other proteins that were endocytosed together. Approximately 80% of endocytosed material is recycled back to the plasma membrane either directly or indirectly via the Golgi apparatus and the remaining 20% is delivered to the lysosome for degradation. Although most pathways have been identified, we still lack understanding on how specificity in sorting of recycling cargos into different pathways is achieved, and how the cell reaches high accuracy of these processes in the absence of clear sorting signals in the bulk of the client proteins. In this review, we will summarize our current understanding of the mechanism behind recycling cargo sorting and propose a model of differential affinities between cargo and cargo receptors/adaptors with regards to iterative sorting in endosomes.

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Identification of new mutations in patients with hereditary spherocytosis by next-generation sequencing

Cited by 37 publications

References 24 publications

Genetic and Clinical Characteristics of Patients With Hereditary Spherocytosis in Hubei Province of China

Genetic and Clinical Characteristics of Patients With Hereditary Spherocytosis in Hubei Province of China

Transcriptome Research of Key Modules and Hub Genes Associated with Primary Myelofibrosis by Weighted Co-expression Network Analysis.

Sorting of cargo in the tubular endosomal network

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