Molecular basis of hereditary elliptocytosis due to protein 4.1 deficiency

N Engl J Med. 1986 Sep 11;315(11):680-5. doi: 10.1056/NEJM198609113151105.


Hereditary elliptocytosis is a heterogeneous group of red-cell disorders characterized morphologically by oval-shaped erythrocytes. It is an infrequent but well-defined cause of hemolytic anemia. To investigate the molecular abnormality in this disorder, we examined the arrangement of the gene encoding protein 4.1, a membrane skeletal protein of human erythrocytes, in an Algerian family with hereditary elliptocytosis and severe hemolytic anemia due to complete deficiency of protein 4.1. Southern blot analysis of genomic DNA from hematologically normal and abnormal members of this family showed that the mutant gene had a DNA rearrangement upstream from the initiation codon for translation. The mRNA from the mutant locus was aberrantly spliced, and that abnormality was the most likely explanation for the deficiency of protein 4.1 in the family. We assigned the gene for erythrocyte protein 4.1 to the short arm (p) of chromosome 1, within a region from band 32 to the terminus (1p32----1pter). Other cases of hereditary elliptocytosis of unknown cause have been mapped to the same region of chromosome 1 by linkage to the Rh locus. The chromosomal location of the gene that codes for protein 4.1 suggests that hereditary elliptocytosis in one class of patients with the disorder may be caused by a mutation of this gene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blood Proteins / deficiency*
  • Blood Proteins / genetics
  • Chromosome Mapping
  • Chromosomes, Human, 1-3
  • Cytoskeletal Proteins*
  • DNA / analysis
  • Elliptocytosis, Hereditary / blood
  • Elliptocytosis, Hereditary / genetics*
  • Erythrocyte Membrane / analysis*
  • Female
  • Humans
  • Male
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics
  • Mutation
  • Neuropeptides*
  • RNA, Messenger / analysis


  • Blood Proteins
  • Cytoskeletal Proteins
  • Membrane Proteins
  • Neuropeptides
  • RNA, Messenger
  • erythrocyte membrane band 4.1 protein
  • erythrocyte membrane protein band 4.1-like 1
  • DNA