β‐Spectrin S<sup>ta</sup> Bárbara: a novel frameshift mutation in hereditary spherocytosis associated with detectable levels of mRNA and a germ cell line mosaicism

Bassères, Daniela S.; Duarte, Adriana Silva Santos; Hassoun, Hani; Costa, Fernando Ferreira; Saad, Sara T. Olalla

doi:10.1046/j.1365-2141.2001.03103.x

Cited by 7 publications

(5 citation statements)

References 24 publications

(23 reference statements)

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“…On the other hand, it cannot be excluded that the truncated protein is degraded or its membrane incorporation is disturbed; in this case, only the normal, full‐length protein would be present in the cell membrane. This kind of situation was reported by Bassères et al (2001) who found that, in an HS subject with detectable levels of SPTB mRNA bearing a premature STOP codon, the mutant protein was undetectable in the erythrocyte membrane.…”

Section: Discussionsupporting

confidence: 53%

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Novel beta‐spectrin mutations in hereditary spherocytosis associated with decreased levels of mRNA

Maciąg¹,

Płochocka²,

Adamowicz-Salach³

et al. 2009

Br J Haematol

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Summary Hereditary spherocytosis (HS) is one of the most frequent and heterogeneous inherited haemolytic anaemias. It is associated with abnormalities of several erythrocyte membrane proteins. We investigated relative mRNA quantification of red blood cell membrane protein genes using real‐time quantitative polymerase chain reaction (qPCR) in order to better characterize HS cases and to select genes to search for mutations in patients with spherocytosis. qPCR experiments indicated that the spectrin β gene (SPTB) could be involved in anaemia pathogenesis. DNA analysis of SPTB in the HS subjects with decreased SPTB mRNA levels revealed the presence of five previously undescribed mutations: R1756X, 781delT and IVS22nt‐4G>A, 1502insA and IVS20nt‐2A>G.

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Section: Discussionsupporting

confidence: 53%

“…The G1408R substitution was first reported by Bassères et al (2001). Since the predicted glycine‐to‐arginine change could potentially be severe, we initially speculated that this genetic change might be responsible for spherocytosis.…”

Section: Discussionmentioning

confidence: 99%

Novel beta‐spectrin mutations in hereditary spherocytosis associated with decreased levels of mRNA

Maciąg¹,

Płochocka²,

Adamowicz-Salach³

et al. 2009

Br J Haematol

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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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“…Bassères DS et al reported a de novo frameshift mutation in the SPTB gene, and they supposed that the mutation might be caused by parental germline mosaicism without further confirmation. 15 In conclusion, mosaicisms pose challenging dilemmas for the diagnosis, prognosis and reproductive counseling of families with individuals affected by mosaic diseases. When parents have a child with constitutional, de novo occurrence of a disorder inherited in autosomal dominant pattern, parental germline or gonosomal mosaicisms must be considered, and they are at risk of passing on the same mutation to future children.…”

Section: Case Reportsmentioning

confidence: 99%

Novel hereditary spherocytosis-associated splice site mutation in the ANK1 gene caused by parental gonosomal mosaicism

et al. 2018

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Hereditary spherocytosis (HS) is a heterogeneous condition of inherited hemolytic anemia characterized by anemia, jaundice, cholelithiasis and splenomegaly with a prevalence of 1 in 10,000 in China 1 . Diagnosis of HS is mainly based on a positive familial history, clinical features and laboratory data, and observation of spherocytes in a peripheral blood smear. -thalassemia genetic mutation screen found no abnormality. Osmotic fragility was increased, and spherocytes were observed in a peripheral blood smear. Both her 28-year-old father and 27-year-old mother were asymptomatic.The available laboratory data are summarized in Table 1.Targeted NGS was performed for DNA extracted from peripheral blood mononuclear cells (PBMCs) of the proband using a panel targeting all exons and adjacent introns of ANK1, EPB42, SLC4A1, SPTA1, and SPTB genes. For the proband, the mean depth was 2,096-fold; 99.00% of the mapped reads were on target, and 98.41% of the target bases were covered at least 20 times. The mean uniformity of base coverage was 95.07%. 97 variants were identified in the proband, distributed in exons, introns, 3′-UTR, 5′-UTR and splice site. These variants were filtered according to mutation type, amino acid alteration, effect on reading frame, minor allele frequency in 1000G, ExAC, dbSNP, ClinVar, and gnomAD databases, records in the HGMD database, and mutation functional prediction. After filtration, a novel heterozygous ANK1 c.3084-2A>G (NM_001142446.1) splice site mutation (covered by 1286-fold) was selected for further validation by Sanger sequencing, and the ANK1 c.3084-2A>G mutation was not found in the 1000G, dbSNP, ClinVar, ExAC, gnomAD, or HGMD databases. Sanger sequencing confirmed the heterozygous ANK1 c.3084-2A>G mutation in the proband. Genetic screening within the family members revealed that this mutation was absent from her mother. However, her father's chromatogram showed a small peak of G within the A reference nucleotide at the ANK1 c.3084-2 position, which was repeated in a buccal swab sample and was more obvious in his sperm (Figure 1). These results suggest the probability of germline and somatic mosaicism for the proband's father. To evaluate this hypothesis, NGS was further performed for DNA from PBMCs, the buccal swab, and the sperm of her father. The ANK1 c.3084-2A>G mutation (chr8:41552851) was present at 16%, 15%, and 29% with 735-, 745-, and 901-fold sequence coverage for PBMCs, the buccal swab, and sperm, respectively, providing evidence of germline and somatic mosaicism. Buccal mucosa may contain variable contamination of leukocytes. Taken together, her father was a combination of germline and somatic mosaicism, and the proband's constitutional ANK1 c.3084-2A>G mutation was caused by her father's mutant germline cells.To explore the splice site effect of the ANK1 c.3084-2A>G mutation (located in intron 27), mRNA of PBMCs was isolated from the family members and reverse transcribed into cDNA. Primers covering exon 27 to exon 29 to generate a 624 nucleotide PCR product were used. A...

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β‐Spectrin S^ta Bárbara: a novel frameshift mutation in hereditary spherocytosis associated with detectable levels of mRNA and a germ cell line mosaicism

Cited by 7 publications

References 24 publications

Novel beta‐spectrin mutations in hereditary spherocytosis associated with decreased levels of mRNA

Novel beta‐spectrin mutations in hereditary spherocytosis associated with decreased levels of mRNA

Mutational characteristics of ANK1 and SPTB genes in hereditary spherocytosis

Novel hereditary spherocytosis-associated splice site mutation in the ANK1 gene caused by parental gonosomal mosaicism

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β‐Spectrin Sta Bárbara: a novel frameshift mutation in hereditary spherocytosis associated with detectable levels of mRNA and a germ cell line mosaicism

Cited by 7 publications

References 24 publications

Novel beta‐spectrin mutations in hereditary spherocytosis associated with decreased levels of mRNA

Novel beta‐spectrin mutations in hereditary spherocytosis associated with decreased levels of mRNA

Mutational characteristics of ANK1 and SPTB genes in hereditary spherocytosis

Novel hereditary spherocytosis-associated splice site mutation in the ANK1 gene caused by parental gonosomal mosaicism

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β‐Spectrin S^ta Bárbara: a novel frameshift mutation in hereditary spherocytosis associated with detectable levels of mRNA and a germ cell line mosaicism