A variant of the <i>EPB3</i> gene of the anti‐Lepore type in hereditary spherocytosis

Bianchi, Paola; Zanella, Alberto; Alloisio, Nicole; Barosi, Giovanni; Bredi, Elena; Pasqui, Gabriele; Zappa, Manuela; Vercellati, Cristina; Baronciani, Luciano; Delaunay, Jean; Sirchia, G.

doi:10.1046/j.1365-2141.1997.1983013.x

Cited by 20 publications

(12 citation statements)

References 22 publications

(38 reference statements)

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“…13 A 69 nucleotide duplication comprising 7 intronic and 62 exonic residues of SLC4A1 encoding anion exchanger member 1 also results in an active upstream copy of the 39 splice sites. 14 Thus, the scanning model of recognition of the 39 splice site applies to most physiological and pathological duplications of the 39 splice sites, though exceptions do occur and await explanation. 10 snRNA is mostly compensated for by a match at position +6 in 1801 human exons.…”

Section: Duplication Of the 39 Splice Sitementioning

confidence: 99%

Spectrum of splicing errors caused by CHRNE mutations affecting introns and intron/exon boundaries

Ohno

Tsujino

et al. 2005

Journal of Medical Genetics

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Background: Mutations in CHRNE, the gene encoding the muscle nicotinic acetylcholine receptor e subunit, cause congenital myasthenic syndromes. Only three of the eight intronic splice site mutations of CHRNE reported to date have had their splicing consequences characterised. Methods: We analysed four previously reported and five novel splicing mutations in CHRNE by introducing the entire normal and mutant genomic CHRNEs into COS cells. Results and conclusions: We found that short introns (82-109 nucleotides) favour intron retention, whereas medium to long introns (306-1210 nucleotides) flanking either or both sides of an exon favour exon skipping. Two mutations are of particular interest. Firstly, a GRT substitution at the 39 end of exon 8 predicts an R286M missense mutation, but instead results in skipping of exon 8. In human genes, a mismatch of the last exonic nucleotide to U1 snRNP is frequently compensated by a matching nucleotide at intron position +6. CHRNE intron 8 has a mismatch at position +6, and accordingly fails to compensate for the exonic mutation at position -1. Secondly, a 16 bp duplication, giving rise to two 39 splice sites (g.IVS10-9_c.1167dup16), results in silencing of the downstream 39 splice site. This conforms to the scanning model of recognition of the 39 splice site, which predicts that the first "ag" occurring after the branch point is selected for splicing.

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Section: Duplication Of the 39 Splice Sitementioning

confidence: 99%

Spectrum of splicing errors caused by CHRNE mutations affecting introns and intron/exon boundaries

Ohno

Tsujino

et al. 2005

Journal of Medical Genetics

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“…In band 3 Benesov, Birmingham, Chur, Most, Napoli II, Okinawa and Philadelphia, other highly conserved amino acids crucial for stabilization of band 3 within the lipid layer are substituted (Maillet et al , 1995; Kanzaki et al , 1997; Miraglia del Giudice et al , 1997b). A 22‐residue insertion in the transmembrane domain in band 3 Milano prevents incorporation of the peptide into the membrane (Bianchi et al , 1997), and a single amino acid deletion in the transmembrane domain is found in band 3 Osnabrück II (Eber et al , 1996).…”

Section: Hereditary Spherocytosis Is Caused By Defective Vertical Intmentioning

confidence: 99%

Red blood cell membrane disorders

1999

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The red blood cell membrane is a multi-component structure that is responsible for many of the physiological functions and mechanical properties of the cell. Defects in any of these components can manifest as clinical disorders involving the erythrocytes. In the past few years there have been major advances in our understanding of the molecular basis of these disorders, in which mutational analysis has clarified many questions about the structure-function relationship of components of the red cell membrane. Some of these recent findings will be the subject of this review. A detailed discussion of the structure of the red cell membrane and the pathophysiology and clinical aspects of its disorders can be found in several recent reviews

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“…The 5006 bp deletion might originate from a misalignment of the two alleles during crossing over in meiosis, as hypothesized for PK ‘Gypsy’ (Baronciani & Beutler, 1995) and in other inherited red cell defects (Nicholls et al , 1987; Bianchi et al , 1997). At the extremity of the deleted fragment we found two 4 bp identical sequences (tggc), in intron 3 and in exon 10 respectively that might have caused this unequal recombination event.…”

Section: Discussionmentioning

confidence: 95%

Red cell pyruvate kinase deficiency: 17 new mutations of the PK‐LR gene

et al. 2005

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Summary The PK‐LR gene was studied in 23 patients with congenital haemolytic anaemia associated with erythrocyte pyruvate kinase (PK) deficiency. Twenty‐seven different mutations were detected among the 42 mutated alleles identified: 19 missense mutations, four splice site mutations and one nonsense, one single base deletion and two large deletions. Seventeen of them (107G, 278T, 403T, 409A, 661A, 859C, 958A, 1094T, 1190T, 1209A, 1232C, 1369G, 507A, IVS9 −1c, IVS9 +43t, del C224, del 5006bp IVS3→ nt 1431) were new. Although all the exons, the flanking regions and the promoter were sequenced in all cases, we failed to detect the second expected mutation in four subjects. To correlate genotype to phenotype, the molecular results were related to the biochemical properties of the mutant enzymes by an analysis of the three‐dimensional structure of erythrocyte PK. The new mutant 409A, found in association with the large deletion of 5006 bp in a newborn baby who died soon after birth, was functionally characterized by mutagenesis and in vitro expression of the protein to investigate its contribution in the severity of the clinical pattern. However, the biochemical data obtained for the mutant enzyme cannot explain the severe anaemia found in the PK‐deficient patient hemizygous for this mutation.

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A variant of the EPB3 gene of the anti‐Lepore type in hereditary spherocytosis

Cited by 20 publications

References 22 publications

Spectrum of splicing errors caused by CHRNE mutations affecting introns and intron/exon boundaries

Spectrum of splicing errors caused by CHRNE mutations affecting introns and intron/exon boundaries

Red blood cell membrane disorders

Red cell pyruvate kinase deficiency: 17 new mutations of the PK‐LR gene

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