-spectrinBari: a truncated  -chain responsible for dominant hereditary spherocytosis

Perrotta, Silverio; Ragione, Fulvio Della; Avvisati, Rosa Anna; Pinto, Daniela Di; Mieri, Giovanna De; Scianguetta, Saverio; Mancusi, Silvia; Falco, Luigia De; Marano, Vito; Iolascon, Achille

doi:10.3324/haematol.2009.010124

Cited by 11 publications

(9 citation statements)

References 24 publications

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“…After a literature search related to HS, 50 cases including 31 ANK1 and 19 SPTB mutations were identified. These reports provided laboratory and clinical data, such as Hb level, splenectomy, and aplastic crisis which allowed calculation of the difference of Hb level according to mutated genes or the frequencies of splenectomy and aplastic crisis according to located domain of mutation in each gene.…”

Section: Resultsmentioning

confidence: 99%

Mutational characteristics of ANK1 and SPTB genes in hereditary spherocytosis

et al. 2016

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The aim of this study was to describe the mutational characteristics in Korean hereditary spherocytosis (HS) patients. Relevant literatures including genetically confirmed cases with well-documented clinical summaries and relevant information were also reviewed to investigate the mutational gene- or domain-specific laboratory and clinical association. Twenty-five HS patients carried one heterozygous mutation of ANK1 (n = 13) or SPTB (n = 12) but not in SPTA1, SLC4A1, or EPB42. Deleterious mutations including frameshift, nonsense, and splice site mutations were identified in 91% (21/23), and non-hotspot mutations were dispersed across multiple exons. Genotype-phenotype correlation was clarified after combined analysis of the cases and the literature review; anemia was most severe in HS patients with mutations on the ANK1 spectrin-binding domain (p < 0.05), and SPTB mutations in HS patients spared the tetramerization domain in which mutations of hereditary elliptocytosis and pyropoikilocytosis are located. Splenectomy (17/75) was more frequent in ANK1 mutant HS (32%) than in HS with SPTB mutation (10%) (p = 0.028). Aplastic crisis occurred in 32.0% of the patients (8/25; 3 ANK1 and 5 SPTB), and parvovirus B19 was detected in 88%. The study clarifies ANK1 or SPTB mutational characteristics in HS Korean patients. The genetic association of laboratory and clinical aspects suggests comprehensive considerations for genetic-based management of HS.

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Section: Resultsmentioning

confidence: 99%

Mutational characteristics of ANK1 and SPTB genes in hereditary spherocytosis

et al. 2016

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“…Relative mRNA quantification can be used to analyse gene expression studies using suitable internal reference genes. On analysing the ΔCt values from patient v/s healthy controls we found significant changes in the ANK1 and SPTB genes in HS patients in comparison to healthy controls (Maciąg et al , ; Perrotta et al , ), indicating the presence of variants in mostly in these genes in our patients.…”

Section: Discussionmentioning

confidence: 54%

“…Quantification of erythrocyte membrane proteins has been used in various studies to find the causative defects in HS patients at the protein level (Perrotta et al , ). Most of the previous studies had used this method as a biochemical method to facilitate detection of the underlying genetic defect in HS, but we did not find this technique to be a sensitive enough to further target the gene of interest to find the variants (Nakanishi et al , ; Canbolat Ayhan et al , ).…”

Section: Discussionmentioning

confidence: 99%

Deciphering molecular heterogeneity of Indian families with hereditary spherocytosis using targeted next‐generation sequencing: First South Asian study

et al. 2019

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Summary Defects in various erythrocyte membrane proteins genes (ankyrin, band‐3, β‐ and α‐spectrin and protein 4·2) can cause hereditary spherocytosis (HS). This molecular heterogeneity of HS, together with co‐inherited genetic modifiers, results in marked phenotypic variability among patients. We studied the molecular spectrum and genotype‐phenotype correlations in 73 families (with 113 patients) with HS. Deleterious variants including nonsense (42%), deletions (18%), splice site (20%), missense (10%) and duplication/insertion (10%) were found in 47 patients. The variants detected included sporadic and dominantly‐inherited defects in ANK1 (53·2%), SPTB (36·2%) and SLC4A1 (4·2%). Compound heterozygous variants in SPTA1 (6·4%) showed autosomal recessive inheritance. Alpha‐spectrin variants were associated with severe anaemia and splenectomy alleviated symptoms. Co‐inherited glucose‐6‐phosphate dehydrogenase (G6PD) deficiency was found in 15%. G6PD variants (n = 5) led to greater transfusion requirements (1‐8 times) in males with HS. Homozygosity (41%) for the promoter variant of UGT1A1 (Gilbert syndrome) led to a significantly higher mean bilirubin level (126·54 µmol/l) with a higher frequency of cholelithiasis (30%) (P < 0·001). This first‐ever south Asian study on the molecular spectrum of HS found ANK1 and SPTB genes variants to be the commonest with inheritance being sporadic/dominant. Next‐generation sequencing provided a relatively sensitive and rapid tool for molecular diagnosis with a diagnostic yield of 64·4%.

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“…The main RBC membrane protein-encoding genes include SPTA1, SPTB, ANK1, SLC4A1 and EPB42, and the corresponding proteins they encode include α-spectrin, β-spectrin, ankyrin, band 3 and 4.2 protein, respectively. Previous studies have shown that the severity of HS is associated with the type of membrane protein defect in the patient (26). Specifically, patients with defects in α-spectrin present with severe anemia, while those with defects in ankyrin, band 3 and 4.2 protein present with mild to moderate anemia (27).…”

Section: Discussionmentioning

confidence: 99%

Analysis of the causes of the misdiagnosis of hereditary spherocytosis

et al. 2018

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Hereditary spherocytosis (HS) is an inherited hemolytic disease with clinical diversities. The aim of the present study was to examine the reasons for prolonged misdiagnosis and mistherapy of HS in a Chinese patient, and to summarize the laboratory screening and treatment methods for this disease in increasing the knowledge towards HS. Clinical data of the proband was reviewed. The proband was first screened by detection of eosin-5'-maleimide (EMA)-labeled red blood cells (RBCs) using flow cytometry. The type of protein defect in the extracted RBC membrane proteins was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Mutant fragments were verified using direct DNA sequencing and matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectroscopy. The proband showed a significant hemolytic tendency and significant reduction in the number of EMA-labeled RBCs. DNA sequencing indicated three site mutations in the SPTA1 gene, including His54Pro, Leu1858Val and 6531-12C>T. Additional DNA analysis of the three mutations in the parents of the proband showed that both the Leu1858Val and 6531‑12C>T mutations were carried by the father and the His54Pro mutation was carried by the mother. Moreover, the mutated peptides were identified by MALDI-TOF mass spectroscopy. HS has diverse clinical manifestations and is easily missed, misdiagnosed and mistreated. Therefore, a comprehensive analysis involving a routine blood test, blood smear, EMA labeling (flow cytometry) and SDS-PAGE can effectively distinguish HS from thalassemia, glucose-6-phosphate deficiency, iron-deficiency anemia and autoimmune hemolytic anemia.

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-spectrinBari: a truncated -chain responsible for dominant hereditary spherocytosis

Cited by 11 publications

References 24 publications

Mutational characteristics of ANK1 and SPTB genes in hereditary spherocytosis

Mutational characteristics of ANK1 and SPTB genes in hereditary spherocytosis

Deciphering molecular heterogeneity of Indian families with hereditary spherocytosis using targeted next‐generation sequencing: First South Asian study

Analysis of the causes of the misdiagnosis of hereditary spherocytosis

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