MOLECULAR DIAGNOSIS OF ACUTE INTERMITTENT PORPHYRIA BY ANALYSIS OF DNA EXTRACTED FROM HAIR ROOTS

Analysis for mutations in the porphobilinogen deaminase gene offers a more definitive diagnosis of acute intermittent porphyria (AIP) than d o conventional biochemical tests. We used single-strand conformation p olymorphism 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 ident ify other individuals who inherited this mutation, we analyzed five ha irs with intact roots collected by each participating family member an d sent to us by mail. DNA was extracted from the hair roots and amplif ied by the polymerase chain reaction. The amplified products were dige sted with the restriction enzyme BsaJl to confirm the presence or abse nce of the mutation. All six family members who were known to have AIP tested positive, as did three members who had not been previously dia gnosed. Hair roots provide a convenient, accessible, and economical al ternative to blood as a source of DNA for molecular diagnostic testing .