Abstract
The aims of our research were to define the genotype–phenotype correlations of mutations in the phenylalanine hydroxylase (PAH) gene that cause phenylketonuria (PKU) among the Israeli population. The mutation spectrum of the PAH gene in PKU patients in Israel is described, along with a discussion on genotype–phenotype correlations. By using polymerase chain reaction/denaturing high-performance liquid chromatography (PCR/dHPLC) and DNA sequencing, we screened all exons of the PAH gene in 180 unrelated patients with four different PKU phenotypes [classic PKU, moderate PKU, mild PKU, and mild hyperphenylalaninemia (MHP)]. In 63.2% of patient genotypes, the metabolic phenotype could be predicted, though evidence is also found for both phenotypic inconsistencies among subjects with more than one type of mutation in the PAH gene. Data analysis revealed that about 25% of patients could participate in the future in (6R)-l-erythro-5, 6, 7, 8-tetrahydrobiopterin (BH4) treatment trials according to their mutation genotypes. This study enables us to construct a national database in Israel that will serve as a valuable tool for genetic counseling and a prognostic evaluation of future cases of PKU.
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Acknowledgments
The study was supported in part by grants from The Elsa and Leo Abramson Fund and The Rivka Nacht Fund for Research in Neurology. This study was part of a master’s degree at Tel Aviv University (AE). We also thank the Israeli PKU Family Foundation for their support.
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Bercovich, D., Elimelech, A., Zlotogora, J. et al. Genotype–phenotype correlations analysis of mutations in the phenylalanine hydroxylase (PAH) gene. J Hum Genet 53, 407–418 (2008). https://doi.org/10.1007/s10038-008-0264-4
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DOI: https://doi.org/10.1007/s10038-008-0264-4
