A new mutation within the porphobilinogen deaminase gene leading to a truncated protein as a cause of acute intermittent porphyria in an extended Indian family.

Based on Internet search, we were contact- ed by a 50-year-old man suffering from severe ab- dominal pain. Acute hepatic porphyria was consid- ered from positive Watson-Schwartz test. He, not being a health professional, searched for centres with ability to do molecular diagnosis and for information about therapeutic possibilities. He asked his phy- sician for haem-arginate (Normosang, Orphan Eu- rope, Paris) treatment, arranged sending his blood to our laboratory and mediated genetic counselling for him and his family. Molecular analyses of the PBGD gene revealed a novel mutation in exon 15, the 973insG. Subsequently, genetic analysis was per- formed in 18 members of the proband's extensive family. In 12 members of the family, the same muta- tion was found. The mutation, which consisted of one nucleotide insertion, resulted in addition of four dif- ferent amino acids leading to a protein that is prema- turely truncated by the stop codon. The effect of this mutation was investigated by expression of the wild- type and mutated PBGD in a prokaryotic expression system. The mutation resulted in instability of the protein and loss of enzymatic function. The increas- ing access to a number of disease- and symptom-ori- ented web pages presents a new and unusual venue for gaining knowledge and enabling self-diagnosis and self-help. It is, therefore, important that disease- oriented Internet pages for public use should be de- signed with clarity and accurate current knowledge- based background.