Molecular diagnosis of acute intermittent porphyria by analysis of DNA extracted from hair roots

Clin Chem. 1994 Sep;40(9):1744-8.

Abstract

Analysis for mutations in the porphobilinogen deaminase gene offers a more definitive diagnosis of acute intermittent porphyria (AIP) than do conventional biochemical tests. We used single-strand conformation polymorphism analysis followed by direct sequencing to identify a new G-->A mutation at the last position of intron 7 in a patient with AIP. The mutation disrupts the invariant AG dinucleotide at the 3' splice acceptor site and therefore interferes with mRNA processing. To identify other individuals who inherited this mutation, we analyzed five hairs with intact roots collected by each participating family member and sent to us by mail. DNA was extracted from the hair roots and amplified by the polymerase chain reaction. The amplified products were digested with the restriction enzyme BsaJI to confirm the presence or absence of the mutation. All six family members who were known to have AIP tested positive, as did three members who had not been previously diagnosed. Hair roots provide a convenient, accessible, and economical alternative to blood as a source of DNA for molecular diagnostic testing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA / genetics*
  • DNA / isolation & purification
  • Female
  • Hair / chemistry*
  • Humans
  • Hydroxymethylbilane Synthase / metabolism
  • Male
  • Molecular Sequence Data
  • Pedigree
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Porphyria, Acute Intermittent / diagnosis*
  • Porphyria, Acute Intermittent / enzymology
  • Porphyria, Acute Intermittent / genetics
  • RNA, Messenger / genetics

Substances

  • RNA, Messenger
  • DNA
  • Hydroxymethylbilane Synthase