β Spectrin kissimmee: A spectrin variant associated with autosomal dominant hereditary spherocytosis and defective binding to protein 4.1

Pamela S. Becker, William T. Tse, Samuel E. Lux, Bernard G. Forget

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

We analyzed the DNA sequence of the cDNA encoding the NH2 terminal region of β spectrin from members of a kindred with autosomal dominant hereditary spherocytosis associated with defective protein 4.1 binding. We found a point mutation at codon 202 within the 272 amino acid NH2-terminal region of β spectrin. TGG was changed to CGG, resulting in the replacement of tryptophan by arginine. The base change eliminates a normally occurring PvuII restriction site and creates a new MspI site. This finding enabled rapid detection or exclusion of the mutation at the DNA level among the family members, including one member for whom this analysis was performed prenatally. The mutation was found only in the affected family members and occurred as a de novo mutation in the proband. It has not been found in 20 other kindreds. The recombinant peptide derived from the normal cDNA retains the capacity to sediment with protein 4.1 and F-actin. The mutant peptide spontaneously degrades. This variant represents both the first point mutation and the first β spectrin mutation demonstrated in autosomal dominant hereditary spherocytosis. Furthermore, the mutation is located within a conserved sequence among spectrinlike proteins and may define an amino acid critical for protein 4.1 binding activity.

Original languageEnglish (US)
Pages (from-to)612-616
Number of pages5
JournalJournal of Clinical Investigation
Volume92
Issue number2
DOIs
StatePublished - 1993

Keywords

  • acanthocytes
  • congenital hemolytic anemia
  • cytoskeleton
  • erythrocyte membrane
  • polymerase chain reaction

ASJC Scopus subject areas

  • Medicine(all)

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