In vitro expression analysis of R68G and R68S mutations in phenylalanine hydroxylase gene.

• Authors: Cezary Żekanowski , Belen Perez , Lourdes R Desviat , Wojciech Wiszniewski , Magdalena Ugarte
• Languages of publication: EN

Abstracts

EN

Phenylketonuria (PKU), an autosomal recessive disorder caused be a deficiency of hepatic phenylalanine hydroxylase (PAH), is clinically very heterogeneous. At the molecular level, more than 400 mutations in the PAH gene are known to date, which in different genotype combinations could account for biochemical and clinical variability of symptoms. In vitro expression studies on R68G and R68S mutations causing mild phenylketonuria are presented.

Keywords

EN

phenylalanine hydroxylase; expression analysis; mutation; hyperphenylalaninemia

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2000
• Volume: 47
• Issue: 2
• Pages: 365-369

Dates

published

2000

received

2000-04-18

Contributors

author

Cezary Żekanowski

• Department of Medical Genetics, National Research Institute of Mother and Child, Warszawa, Poland

author

Belen Perez

• Center of Molecular Biology "Severo Ochoa", Autonomous University of Madrid, 28049 Madrid, Spain

author

Lourdes R Desviat

• Center of Molecular Biology "Severo Ochoa", Autonomous University of Madrid, 28049 Madrid, Spain

author

Wojciech Wiszniewski

• Department of Medical Genetics, National Research Institute of Mother and Child, Warszawa, Poland

author

Magdalena Ugarte

• Center of Molecular Biology "Severo Ochoa", Autonomous University of Madrid, 28049 Madrid, Spain

References

• 1. Koch, R., Fishler, K., Azen, C., Gouldberg, P. & Guttler, F. (1997) The relationship of genotype to phenotype in phenylalanine hydroxylase deficiency. Biochem. Mol. Med. 60, 92- 101.
• 2. Eisensmith, R.C., Martinez, B.S., Kuzmin, A.I., Goltsov, A.A., Brown, A., Singh, R., Elssas, L.J. & Woo, S.L.C. (1996) Molecular basis of phenylketonuria and correlation between genotype and phenotype in heterogeneous southeastern US population. Pediatrics 97, 512-516.
• 3. Desviat, L.R., Perez, B., Garcia, M.J., Martinez-Pardo, M., Beldellou, A., Arena, J., Sanjurjo, P., Campistol, J., Couce, M.L., Fernandez, A., Cardesa, J. & Ugarte, M. (1997) Relationship between mutations and genotype and biochemical phenotype in a heterogenous Spanish population. Eur. J. Hum. Genet. 5, 196-202.
• 4. Desviat, L.R., Perez, B., Gamez, A., Sanchez, A., Garcia, M.J., Martinez-Pardo, M., Marchante, C., Boveda, D., Beldellou, A., Arena, J., Sanjurjo, P., Fernandez, A., Cabello, M.L. & Ugarte, M. (1999) Genetic and phenotypic aspects of phenylalanine hydroxylase deficiency in Spain: Molecular survey by regions. Eur. J. Hum. Genet. 7, 386-392.
• 5. Żekanowski, C., Nowacka, M., Giżewska, M., Filipowicz, J., Cabalska, B. & Bal, J. (1999) Mutations in exon 3 of the PAH gene causing mild hyperphenylalaninemia. Genet Test. 3, 297-299.
• 6. De Lucca, M., Perez, B., Desviat, L.R. & Ugarte, M. (1998) Molecular basis of phenylketonuria in Venezuela: Presence of two novel null mutations. Hum Mutat. 11, 354-359.
• 7. Martinez, A., Knappskog, P.M., Olafdotti, S., Doskeland, A.P., Eiken, H.G., Svebak, R.M., Bozzini, M., Apold, J. & Flatmark, T. (1995) Expression of recombinant human phenylalanine hydroxylase as fusion protein in Escherichia coli circumvents proteolytic degradation by host cell proteases. Biochem. J. 306, 589- 597.
• 8. Perez, B., Desviat, L.R. & Ugarte, M. (1995) Expression analysis of mutation P244L which cause mild hyperphenylalaninemia. Hum. Mutat. 5, 188-190.
• 9. Desviat, L.R., Perez, B. & Ugarte, M. (1996) Molecular basis of non-PKU hyperphenylalaninemia in Spain: Prevalence of A403V, a mutation with high residual activity. J. Inherit. Metab. Dis. 19, 227-230.
• 10. Knappskog, P.M., Eiken, H.G., Martinez, A., Bruland, O., Apold, J. & Flatmark, T. (1996) A PKU mutation (D143G) associated with an apparent high residual enzyme activity: Expression of a kinetic variant form of phenylalanine hydroxylase in three different systems. Hum. Mutat. 8, 236-246.
• 11. Kayaalp, E., Treacy, E., Waters, P.J., Byck, S., Nowacki, P. & Scriver, C.R. (1997) Human phenylalanine hydroxylase mutations and hyperphenylalaninemia phenotypes: A metanalysis of genotype-phenotype correlations. Am. J. Hum. Genet. 61, 1309-1317.
• 12. Waters, P.J., Parniak, M.A., Nowacki, P. & Scriver, C.R. (1998) In vitro expression analysis of mutations in phenylalanine hydroxylase: Linking genotype to phenotype and structure to function. Human Mutat. 11, 4-17.