Should genetic analysis in newborn screening and a heterozygote test for hyperphenylalaninaemia be recommended? An italian study

A. Rottoli, M. L. Gianní, E. Verduci, M. L. Biondi, L. Fiori, M. Giovannini, E. Riva

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objective - To determine whether the introduction of genetic analysis for phenylalanine hydroxylase (PAH) deficiency into regional screening programmes can be supported by the benefit-cost ratio. Method - Tests for the genetic PAH locus were carried out in 151 patients with hyperphenylalaninaemia originally from all of the Italian regions. PAH mutations were identified by extraction of genomic DNA from leucocytes (whole blood in EDTA), PAH exon amplification was determined by polymerase chain reaction, restriction enzyme analysis was carried out for some recognised mutations, and DNA sequence analysis for the other mutations. Results - It was found that the eight most common mutations in the population accounted for 49% of the mutant alleles, which is well below the required standard for effective population screening (90%). Conclusions - Genetic screening for PAH deficiency in Italy does not increase the sensitivity of the methodology and the benefit-cost ratio, and thus provides no advantage, particularly as the correlation between genotype and the metabolic phenotype needed to optimise dietary intervention is still being studied.

Original languageEnglish
Pages (from-to)193-194
Number of pages2
JournalJournal of Medical Screening
Volume6
Issue number4
Publication statusPublished - 1999

Fingerprint

Phenylketonurias
Phenylalanine Hydroxylase
Heterozygote
Newborn Infant
Mutation
Cost-Benefit Analysis
Restriction Mapping
Genetic Testing
DNA Sequence Analysis
Edetic Acid
Italy
Population
Exons
Leukocytes
Alleles
Genotype
Phenotype
Polymerase Chain Reaction
DNA

Keywords

  • Genetic screening
  • Heterozygote test
  • Hyperphenylalaninaemia

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health

Cite this

Should genetic analysis in newborn screening and a heterozygote test for hyperphenylalaninaemia be recommended? An italian study. / Rottoli, A.; Gianní, M. L.; Verduci, E.; Biondi, M. L.; Fiori, L.; Giovannini, M.; Riva, E.

In: Journal of Medical Screening, Vol. 6, No. 4, 1999, p. 193-194.

Research output: Contribution to journalArticle

Rottoli, A. ; Gianní, M. L. ; Verduci, E. ; Biondi, M. L. ; Fiori, L. ; Giovannini, M. ; Riva, E. / Should genetic analysis in newborn screening and a heterozygote test for hyperphenylalaninaemia be recommended? An italian study. In: Journal of Medical Screening. 1999 ; Vol. 6, No. 4. pp. 193-194.
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AU - Verduci, E.

AU - Biondi, M. L.

AU - Fiori, L.

AU - Giovannini, M.

AU - Riva, E.

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AB - Objective - To determine whether the introduction of genetic analysis for phenylalanine hydroxylase (PAH) deficiency into regional screening programmes can be supported by the benefit-cost ratio. Method - Tests for the genetic PAH locus were carried out in 151 patients with hyperphenylalaninaemia originally from all of the Italian regions. PAH mutations were identified by extraction of genomic DNA from leucocytes (whole blood in EDTA), PAH exon amplification was determined by polymerase chain reaction, restriction enzyme analysis was carried out for some recognised mutations, and DNA sequence analysis for the other mutations. Results - It was found that the eight most common mutations in the population accounted for 49% of the mutant alleles, which is well below the required standard for effective population screening (90%). Conclusions - Genetic screening for PAH deficiency in Italy does not increase the sensitivity of the methodology and the benefit-cost ratio, and thus provides no advantage, particularly as the correlation between genotype and the metabolic phenotype needed to optimise dietary intervention is still being studied.

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