The STR252 - IVS10nt546 - VNTR7 phenylalanine hydroxylase minihaplotype in five mediterranean samples

Francesco Calì, Irma Dianzani, Lourdes R. Desviat, Belen Perez, Magdalena Ugarte, Meral Ozguc, Volkan Seyrantepe, Yossi Shiloh, Sergio Giannattasio, Carla Carducci, Paolo Bosco, Giacomo De Leo, Alberto Piazza, Valentino Romano*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


IVS10nt546 (IVS10nt-llg→a) is the most common molecular defect of the phenylalanine hydroxylase gene causing phenylketonuria in Mediterranean populations. Previous studies have proposed various and alternative hypotheses concerning the geographical origin and pattern of diffusion of this mutation in this area. In this study, this issue was re-examined on a large sample (149) of 'Mediterranean' IVS10nt546 mutant alleles analysed with multiallelic intragenic polymorphisms. The analysis of intragenic microsatellite (STR) and minisatellite (VNTR) polymorphisms shows allelic heterogeneity of the IVS10nt546 mutation. Eight STR and three VNTR alleles were found in association with the splicing defect. Of the ten detected STR-VNTR combinations ('minihaplotypes'), we identified a predominant allelic association (VNTR7 - STR252) embedded in a RFLP-haplotype 6 background, which seems to correspond to the ancestral gene originating in the Turkey-Israel area. Analysis of both absolute and relative gene frequencies of the STR252 IVS10nt546 - VNTR7 minihaplotypes, shows statistically significant (P < 0.02) variations and may suggest gene flow from Turkey and/or Israel to Italy and Spain. The associated migratory events need not be unique in time (and people) but seem to suggest they may be traced back to the expansion of the Neolithic culture and people, thus allowing dating of the origin of this mutation to at least 5000-10,000 years ago. Alternative hypotheses are discussed to explain, in light of the available historical and pre-historical evidence, the pattern of diffusion of the IVS10nt546 mutation in the Mediterranean basin.

Original languageEnglish
Pages (from-to)350-355
Number of pages6
JournalHuman Genetics
Issue number3-4
StatePublished - 1997


FundersFunder number
European Commission TMRER-BCHRXCT92003
Italian Ministry of HealthICS-190.1/TC/95.58
Progetto di Ricerca Corrente
Consiglio Nazionale delle Ricerche


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