title: 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.
abstract: Based on Internet search, we were contacted by a 50-year-old man suffering from severe abdominal pain. Acute hepatic porphyria was considered 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 physician for haem-arginate (Normosang, Orphan Europe, 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 performed in 18 members of the proband's extensive family. In 12 members of the family, the same mutation was found. The mutation, which consisted of one nucleotide insertion, resulted in addition of four different amino acids leading to a protein that is prematurely truncated by the stop codon. The effect of this mutation was investigated by expression of the wildtype and mutated PBGD in a prokaryotic expression system. The mutation resulted in instability of the protein and loss of enzymatic function. The increasing access to a number of disease- and symptom-oriented web pages presents a new and unusual venue for gaining knowledge and enabling self-diagnosis and self-help. It is, therefore, important that diseaseoriented Internet pages for public use should be designed with clarity and accurate current knowledge based background.
authors: Department of Pediatrics and Center for Integrated Genomics, Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic.
authors: E
authors: E
authors: Flachsová
authors: I C
authors: IC
authors: Verma
authors: D
authors: D
authors: Ulbrichová
authors: R
authors: R
authors: Saxena
authors: J
authors: J
authors: Zeman
authors: V
authors: V
authors: Saudek
authors: C S
authors: CS
authors: Raman
authors: P
authors: P
authors: Martásek
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005190:Family; D005260:Female; D006418:Heme / Q000378:metabolism; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000737:chemistry / Q000235:genetics*; D007194:India; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D017118:Porphyria, Acute Intermittent / Q000201:enzymology* / Q000235:genetics*; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins
chemical_list: D050505:Mutant Proteins; D011993:Recombinant Fusion Proteins; D006418:Heme; D011163:Hydroxymethylbilane Synthase