Multiple origins for phenylketonuria in Europe

Journal Article · Tue Dec 01 00:00:00 EST 1992 · American Journal of Human Genetics; (United States)

OSTI ID:6717491

Eisensmith, R C; Okano, Y; Dasovich, M; Wang, T; Woo, S L.C. ^[1]; Guettler, F; Lou, H; Guldberg, P ^[2]; Lichter-Konecki, U; Konecki, D S ^[3]; Svensson, E; Hagenfeldt, L ^[4]; Rey, F; Munnich, A; Lyonnet, S ^[5]; Cockburn, F; Connor, J M ^[6]; Pembrey, M E; Smith, I ^[7]; Gitzelmann, R ; Steinmann, B ^[8]; Apold, J; Eiken, H G ^[9]; Giovannini, M; Riva, E; Longhi, R ^[10]; Romano, C; Cerone, R ^[11]; Naughten, E R; Mullins, C; Cahalane, S ^[12]; Oezalp, I ^[13]

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1. Baylor College of Medicine, Houston, TX (United States)
2. John F. Kennedy Inst., Glostrup (Denmark)
3. Universitaets-Kinderklinik, Heidelberg (Germany)
4. Huddinge University Hospital (Sweden)
5. Hopital des Enfants-Malades, Paris (France)
6. Univ. of Glasgow (United Kingdom)
7. Univ. of London (United Kingdom)
8. Universitaets-Kinderklinik, Zuerich (Switzerland)
9. Universitet i Bergen (Norway)
10. Universita Degli Studi Di Milano, Milan (Italy)
11. Universita Di Genova, Genoa (Italy)
12. Children's Hospital, Dublin (Ireland)
13. Hacettepe Univ., Ankara (Turkey)

Phenylketonuria (PKU), a disorder of amino acid metabolism prevalent among Caucasians and other ethnic groups, is caused primarily by a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH). PKU is a highly heterogeneous disorder, with more than 60 molecular lesions identified in the PAH gene. The haplotype associations, relative frequencies, and distributions of five prevalent PAH mutations (R158Q, R261Q, IVS10nt546, R408W, and IVS12nt1) were established in a comprehensive European sample population and subsequently were examined to determine the potential roles of several genetic mechanisms in explaining the present distribution of the major PKU alleles. Each of these five mutations was strongly associated with only one of the more than 70 chromosomal haplotypes defined by eight RFLPs in or near the PAH gene. These findings suggest that each of these mutations arose through a single founding event that occurred within time periods ranging from several hundred to several thousand years ago. From the significant differences observed in the relative frequencies and distributions of these five alleles throughout Europe, four of these putative founding events could be localized to specific ethnic subgroups. Together, these data suggest that there were multiple, geographically and ethnically distinct origins for PKU within the European population. 63 refs., 2 figs., 3 tabs.

• OSTI ID: 6717491
• Journal Information: American Journal of Human Genetics; (United States), Vol. 51:6; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
METABOLIC DISEASES
HYDROXYLASES
PHENYLALANINE
DISTRIBUTION
EUROPE
GENETIC VARIABILITY
HUMAN POPULATIONS
METABOLISM
MUTATIONS
RFLPS
BIOLOGICAL VARIABILITY
CARBOXYLIC ACIDS
DISEASES
ENZYMES
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDOREDUCTASES
POPULATIONS
PROTEINS
550400* - Genetics