Summary
The incidence of phenylketonuria (PKU) in the western part of Poland is 1 in 5000 live births. Restriction fragment length polymorphism (RFLP) haplotypes at the phenylalanine hydroxylase locus have been analysed in 46 Polish families with PKU. Among 43 fully-informative families 16 RFLP haplotypes were identified. Haplotype 2 is the most frequently (62%) associated with Polish PKU alleles, and the codon 408 mutation is in complete linkage disequilibrium with this haplotype in Poland. This finding is in agreement with observations in other eastern European countries (German Democratic Republic, Czechoslovakia, and Hungary) and in contrast to the genotype distribution observed in western European countries. The present observation suggests the spread of classical PKU, due to the codon 408 mutation associated with haplotype 2, from east to west in European populations. Perhaps more important for genetic counselling, 62% of all PKU chromosomes in the Polish population can now be detected using only one mutantspecific oligonucleotide probe.
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Chakraborty R, Lidsky AS, Daiger SP, Güttler F, Sullivan S, Di Lella AG, Woo SLC (1987) Polymorphic DNA haplotypes at the human phenylalanine hydroxylase locus and their relationship with phenylketonuria. Hum Genet 76:40–46
Daiger SP, Chakraborty R, Reed L, Fekete G, Schuler D, Berenssi G, Nasz I, Brdicka R, Kamarýt J, Pijácková A, Moore S, Sullivan S, Woo SLC (1989) Polymorphic DNA haplotypes at the phenylalanine hydroxylase (PAH) locus in European families with phenylketonuria (PKU). Am J Hum Genet 45:310–318
DiLella AG, Marvit J, Lidsky AS, Güttler F, Woo SLC (1986) Tight linkage between a splicing mutation and a specific DNA haplotype in phenylketonuria. Nature 322:799–803
DiLella AG, Marvit J, Brayton K, Woo SLC (1987) An aminoacid substitution involved in phenylketonuria is in linkage disequilibrium with DNA haplotype 2. Nature 327:333–336
DiLella AG, Huang WM, Woo SLC (1988) Screening for phenyl-ketonuria mutations by DNA amplification with the polymerase chain reaction. Lancet 1:497–499
Guthrie R, Susi A (1963) A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants. Pediatrics 32:338–343
Güttler F, Woo SLC (1985) Molecular genetics of PKU: prenatal diagnosis and carrier detection by gene analysis. In: Bickel H, Wachtel U (eds) Recent progress in the understanding, recognition and management of inherited disease of amino acid metabolism. Thieme, Stuttgart, pp 18–36
Güttler F, Woo SLC (1986) Molecular genetics of PKU. J Inherited Metab Dis 9 [Suppl 1]: 58–68
Güttler F, Ledley FD, Lidsky AS, DiLella AG, Sullivan SE, Woo SLC (1987a) Correlation between polymorphic DNA haplotypes at phenylalanine hydroxylase locus and clinical phenotypes of phenylketonuria. J Pediatr 110:68–71
Güttler F, DiLella AG, Ledly FD, Lidsky AS, Kwok SCM, Marvit J, Woo SLC (1987b) Molecular biology of phenylketonuria. Eur J Pediatr 146 [Suppl 1]:A5-A11
Hermann FH, Wulff K, Wehnert M, Seidlitz G, Güttler F (1988) Haplotype analysis of classical and mild phenotype of phenylketonuria in the German Democratic Republic. Clin Genet 33:176–180
Hertzberg M, Jahromi K, Ferguson V, Dahl HHM, Mercer J, Mickleson KNP, Trent RJ (1989) Phenylalanine hydroxylase gene haplotypes in Polynesians: evolutionary origins and absence of alleles associated with severe phenylketonuria. Am J Hum Genet 44:382–387
Kwok SCM, Ledley FD, DiLella AG, Robson KJH, Woo SLC (1985) Nucleotide sequence of a full-length complementary DNA clone and amino acid sequence of human phenylalanine hydroxylase. Biochemistry 24:556–561
Ledley FD, Woo SLC (1988) Reconsidering the genetics of phenylketonuria: evidence from molecular genetics. In: Wurtman RJ, Ritter-Walker E (eds) Dietary phenylalanine and brain function. Birkhäuser, Boston Basel, pp 228–237
Levy HL (1989) Molecular genetics of phenylketonuria and its implications. Am J Hum Genet 45:667–670
Lichter-Konecki U, Konecki DS, DiLella AG, Brayton K, Marvit J, Hahn TM, Trefz FK (1988) Phenylalanine hydroxlase deficiency caused by a single base substitution in an exon of the human phenylalanine hydroxylase locus in the German population. Hum Genet 78:347–352
Lidsky AS, Ledley FD, DiLella AG, Kwok SCM, Daiger SP, Robson KJH, Woo SLC (1985) Extensive restriction site polymorphism at the human phenylalanine hydroxylase locus and application in prenatal diagnosis of phenylketonuria. Am J Hum Genet 37:619–634
Lyonnett S, Caillaud C, Rey F, Berthelon M, Frézal J, Rey J, Munnich A (1988) Guthrie cards and needle biopsy of the liver for detection of point mutations in phenylketonuria. Am J Hum Genet 43 [Suppl]:A193
Riess O, Michel A, Speer A, Meiske W, Cobet G, Coutelle C (1988) Linkage disequilibrium between RFLP haplotype 2 and the affected PAH allele in PKU families from the Berlin area of the German Democratic Republic. Hum Genet 78:343–346
Wang T, Okano Y, Eisensmith R, Huang S, Zeng Y, Lo WHY, Woo SLC (1989) Molecular genetics of phenylketonuria in orientals: linkage disequilibrium between a termination mutation and haplotype 4 of phenylalanine hydroxylase gene. Am J Hum Genet 45:675–680
Woo SLC (1988) Collation of RFLP haplotypes at the human henylalanine hydroxylase PAH locus. Am J Hum Genet 43:781–783
Woo SLC, Lidsky AS, Güttler F, Chandra T, Robson KJH (1983) Cloned human phenylalanine hydroxylase gene allows prenatal diagnosis and carrier detection of classical phenylketonuria. Nature 306:151–155
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Jaruzelska, J., Henriksen, K.F., Güttler, F. et al. The codon 408 mutation associated with haplotype 2 is predominant in Polish families with phenylketonuria. Hum Genet 86, 247–250 (1991). https://doi.org/10.1007/BF00202402
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DOI: https://doi.org/10.1007/BF00202402