Exhaustive mutation scanning by fluorescence-assisted mismatch analysis discloses new genotype-phenotype correlations in angiodema

Am J Hum Genet. 1996 Aug;59(2):308-19.


A complete mutational scan of the gene coding for the serpin C1 inhibitor, comprising all eight exons and adjacent intron sequences and 550 bp preceding the transcription start site, was rapidly accomplished in 36 unrelated angioedema patients by using fluorescence-assisted mismatch analysis (FAMA). Mutations accounting for C1 inhibitor deficiency were identified in every one of 34 patients, with two failures turning out to be spurious cases. Two new substitution dimorphisms were also detected in introns. Changes affecting the C1 inhibitor protein, distributed throughout the seven coding exons, provide new insights into the molecular pathology of serpins. Six different splice-site and two promoter mutations were also found. Among the latter, a C-->T transition within one of two putative CAAT boxes of this TATA-less promoter, the sole idiomorphic nucleotide change in this kindred, was found homozygous in the proband, at variance with the dominant mode of transmission observed for structural mutations. FAMA, in the chemical probes configuration used in this study, is a rapid and robust mutation-scanning procedure, applicable to large DNA segments or transcripts and proved capable of 100% detection. Moreover, it provides accurate positional information--and hence recognition of multiple substitutions, precise relationship with those already known, and often immediate identification of the nucleotide change.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angioedema / genetics*
  • Base Sequence
  • Chromosomes, Human, Pair 11
  • Complement C1 Inactivator Proteins / deficiency
  • Complement C1 Inactivator Proteins / genetics*
  • Female
  • Genetic Diseases, Inborn
  • Genetic Testing / methods*
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Peptide Chain Termination, Translational
  • Point Mutation
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • RNA Splicing
  • Repetitive Sequences, Nucleic Acid
  • Sequence Analysis, DNA / methods*
  • Sequence Deletion
  • Serpins / deficiency
  • Serpins / genetics*


  • Complement C1 Inactivator Proteins
  • Serpins