Mutational spectrum of phenylalanine hydroxylase deficiency in Sicily: Implications for diagnosis of hyperphenylalaninemia in Southern Europe

P. Guldberg, V. Romano, N. Ceratto, P. Bosco, M. Ciuna, A. Indelicato, F. Mollica, C. Meli, M. Giovannini, E. Riva, G. Biasucci, K. F. Henriksen, F. Guttler

Research output: Contribution to journalArticle

Abstract

Hyperphenylalaninemia due to a deficiency of hepatic phenylalanine hydroxylase (PAH) is the most common inborn error of amino acid metabolism. Clinical, the disorder is highly heterogeneous, spanning from nonphenylketonuria hyperphenylalaninemia to classical phenylketonuria. Only little is known about the molecular defects underlying hyperphenylalaninemia in Southern Europe. In this study, we conducted a systematic analysis of 53 patients from the Sicilian population. Each patient included in the study had persistently elevated blood levels of phenylananine and met the differential criteria for PAH deficiency. Genomic DNA was analysed by scanning all PAH-coding exons for mutations by PCR in combination with denaturing gradient gel electrophoresis (DGGE). 52 patients were completely genotyped. A spectrum of 40 different mutations was established including 17 novel PAH mutations. Our results explain the clinical heterogeneity of hyperphenylalaninemia in Southern Europe, and form the basis for the establishment of phenotype - genotype correlations in Sicily and surrounding countries.

Original languageEnglish
Pages (from-to)1703-1707
Number of pages5
JournalHuman Molecular Genetics
Volume2
Issue number10
Publication statusPublished - 1993

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ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Genetics(clinical)
  • Public Health, Environmental and Occupational Health

Cite this

Guldberg, P., Romano, V., Ceratto, N., Bosco, P., Ciuna, M., Indelicato, A., Mollica, F., Meli, C., Giovannini, M., Riva, E., Biasucci, G., Henriksen, K. F., & Guttler, F. (1993). Mutational spectrum of phenylalanine hydroxylase deficiency in Sicily: Implications for diagnosis of hyperphenylalaninemia in Southern Europe. Human Molecular Genetics, 2(10), 1703-1707.