Ankyrin Bugey: a de novo deletional frameshift variant in exon 6 of the ankyrin gene associated with spherocytosis

Am J Hematol. 1997 Mar;54(3):242-8. doi: 10.1002/(sici)1096-8652(199703)54:3<242::aid-ajh11>3.0.co;2-f.

Abstract

We describe a case of spherocytosis in a French child splenectomized at age 10 years. The parents were devoid of any clinical, hematological, or biochemical abnormalities. Following splenectomy, the proposita exhibited a reduction of red cell membrane ankyrin. The variable number of dinucleotide repeats associated with the erythroid ankyrin gene (ANK1) were studied at the genomic level. The father, the mother, and the proposita had the AC14/AC11, AC14/AC14, and AC14/AC11 genotypes, respectively, although the proposita exhibited a pattern consistent with an AC14,-combination at the cDNA level. We thought there could be a de novo mutation in the ANK1 allele of paternal origin (AC11). A false paternity seemed most unlikely. Based on PCR-amplification of exons, SSCP analysis, and, when appropriate, nucleotide sequencing, we found a one-nucleotide deletion in codon 146 (exon 6): 521delC, ACG-->AG. This placed in phase a TAG triplet normally overlapping codons 150 and 151. Early interruption of translation presumably accounted for the premature degradation of mutant mRNA. Restriction analysis confirmed the presence of the mutation in the proposita and its absence in the parents. The variant was designated ankyrin Bugey.

Publication types

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

MeSH terms

  • Ankyrins / genetics*
  • Exons / genetics
  • Female
  • Frameshift Mutation*
  • Humans
  • Male
  • RNA, Messenger / analysis
  • Restriction Mapping
  • Spherocytosis, Hereditary / genetics*

Substances

  • Ankyrins
  • RNA, Messenger