A novel mutation causing an aberrant splicing in the protein 4.2 gene associated with hereditary spherocytosis (protein 4.2Notame)

Miho Matsuda, Naoya Hatano, Hiroshi Ideguchi, Hiroyuki Takahira, Yasuyuki Fukumaki

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

We Investigated a Japanese patient with protein 4.2 deficiency. SDS-PAGE showed a complete deficiency of protein 4.2, while Western blot analysis revealed a marked decrease in the amount of protein 4.2, and the existence of a doublet of 74 and 72 kDa bands. Direct sequencing and dot-blot hybridization with allele-specific oligonucleotide probes indicated that the proband was compound heterozygous for a missense mutation in codon 142 with Ala→Thr (GC-T→ACT) and a single nucleotide substitution (G→A) of the first base of intron 6 (G→A) of the protein 4.2 gene. The former is the commonest mutation observed in cases of protein 4.2 deficiency, whereas the latter is a novel mutation, located within the consensus sequence of the 5' splicing site (AGGU) (Protein 4.2Notame). RT-PCR analysis using total RNA isolated from reticulocytes of the proband revealed that the intron 6 donor site mutation causes an abnormal splicing; exon 6 is spliced out with intron 6. The abnormal mRNA has a premature termination codon, as the result of a frameshift, and this instability may lead to degradation. Thus, there is a close relation between this mutation and the molecular pathogenesis of protein 4.2 deficiency. / 1995 Oxford University Press.

Original languageEnglish
Pages (from-to)1187-1191
Number of pages5
JournalHuman Molecular Genetics
Volume4
Issue number7
DOIs
Publication statusPublished - Jul 1 1995

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Protein Splicing
Hereditary Spherocytosis
Protein Deficiency
Introns
Mutation
Proteins
Oligonucleotide Probes
Nonsense Codon
Reticulocytes
Consensus Sequence
Missense Mutation
Codon
Polyacrylamide Gel Electrophoresis
Exons
Nucleotides
Western Blotting
Alleles
Tissue Donors
RNA
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

A novel mutation causing an aberrant splicing in the protein 4.2 gene associated with hereditary spherocytosis (protein 4.2Notame). / Matsuda, Miho; Hatano, Naoya; Ideguchi, Hiroshi; Takahira, Hiroyuki; Fukumaki, Yasuyuki.

In: Human Molecular Genetics, Vol. 4, No. 7, 01.07.1995, p. 1187-1191.

Research output: Contribution to journalArticle

Matsuda, Miho ; Hatano, Naoya ; Ideguchi, Hiroshi ; Takahira, Hiroyuki ; Fukumaki, Yasuyuki. / A novel mutation causing an aberrant splicing in the protein 4.2 gene associated with hereditary spherocytosis (protein 4.2Notame). In: Human Molecular Genetics. 1995 ; Vol. 4, No. 7. pp. 1187-1191.
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