Folia Biologica
Journal of Cellular and Molecular Biology, Charles University 

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Fol. Biol. 2007, 53, 194-201

https://doi.org/10.14712/fb2007053060194

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

E. Flachsová1, I. C. Verma2, D. Ulbrichová1, R. Saxena2, J. Zeman1, V. Saudek3, C. S. Raman4, Pavel Martásek1

1Department of Pediatrics and Center for Integrated Genomics, Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic
2Department of Genetic Medicine, Sir Ganga Ram Hospital, New Delhi, India
3Laboratory of Molecular Pathology, Institute of Inherited Metabolic Disorders, Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic
4Department of Biochemistry, University of Texas, Health Science Center Medical School, Houston, USA

Received September 2007
Accepted September 2007

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 nuc1eotide 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 wild-type 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 disease-oriented Internet pages for public use should be designed with clarity and accurate current knowledge-based background.

Funding

E. F., D. U., J. Z., and P. M., are supported by grants MSM0021620806 and 1M6837805002 from the Ministry of Education, Youth and Sports of the Czech Republic. D. U. is also supported by the Grant Agency of Charles University, GAUK 25754054007.

References

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