{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T05:10:04Z","timestamp":1760764204766,"version":"build-2065373602"},"reference-count":13,"publisher":"BMJ","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1993,3]]},"abstract":"<jats:p>In order to elucidate the clinical homogeneity and severity of the hyperphenylalaninaemias in Poland, a total of 71 children with typical phenylketonuria (PKU) originating from western and northern Poland were screened for 13 mutations in the phenylalanine hydroxylase (PAH) gene. Eighty percent of all PKU alleles tested were found to carry an identified mutation. One mutation, namely the R408W mutation, accounted for more than 63% of mutant PAH alleles in Poland, the other 27% being accounted for by six mutations: IVS12nt1 (5%), IVSnt546 (5%), Y414C (4%), R252W (1.5%), R261Q (&lt; 1%), and G272ter (&lt; 1%). The predominance of the R408W mutation resulted in a high rate of homozygotes (35.2%) and compound heterozygotes for this mutation in children from western and northern Poland. The frequency and deleterious nature of this mutation probably accounts for the clinical homogeneity and severity of the hyperphenylalaninaemias in Poland. In addition, the high rate of the R408W mutation and its association with mutant haplotype 2 at the PAH locus in Poland give additional support to the Balto-Slavic origin of this mutant gene.<\/jats:p>","DOI":"10.1136\/jmg.30.3.232","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:23:16Z","timestamp":1226330596000},"page":"232-234","source":"Crossref","is-referenced-by-count":12,"title":["Genetic background of clinical homogeneity of phenylketonuria in Poland."],"prefix":"10.1136","volume":"30","author":[{"given":"J","family":"Jaruzelska","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Matuszak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Lyonnet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Rey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Rey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Filipowicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Borski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Munnich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1993,3,1]]},"reference":[{"key":"ref_1","first-page":"13","article-title":"Molecular basis of phenylketonuria and related hyperphenylalaninaemias: mutations frequent mutations after R408W are the IVS12ntl (5%) and IVSlOnt546 (5%) mutaand polymorphisms in the human phenylalanine hydroxylase gene","volume-title":"Hum Mutat","volume":"1","author":"Eisensmith, R.C.; Woo, S.L.C.","year":"1992","unstructured":"Eisensmith RC, Woo SLC. 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While no significant linkage disequilibrium could be shown, owing to the small number of mutant alleles, it is worth noting that these mutations mutation associated with haplotype 2 is predominant in Polish families with phenylketonuria. Hum Genet 1991;86:247-50.","journal-title":"Hum Genet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/0888-7543(89)90137-7","article-title":"CpG dinucleotides are mutation hot spots in phenylketonuria","volume":"5","author":"Abadie, V.; Lyonnet, S.; Maurin, N.","year":"1989","unstructured":"Abadie V, Lyonnet S, Maurin N, et al. CpG dinucleotides are mutation hot spots in phenylketonuria. Genomics 1989;5:936-9.","journal-title":"Genomics"},{"key":"ref_4","first-page":"511","article-title":"Molecular genetics of phenylketonuria in Mediterranean countries: a mutation were associated with haplotypes 3 and 6 reassociated with partial phenylalanine hydroxylase defispectively, suggesting that the presence of these mutations in Poland could be related to ciency","volume":"44","author":"Lyonnet, S.; Caillaud, C.; Rey, F.","year":"1989","unstructured":"Lyonnet S, Caillaud C, Rey F, et al. Molecular genetics of phenylketonuria in Mediterranean countries: a mutation were associated with haplotypes 3 and 6 reassociated with partial phenylalanine hydroxylase defispectively, suggesting that the presence of these mutations in Poland could be related to ciency. Am_J Hum Genet 1989;44:511-7.","journal-title":"Am_J Hum Genet"},{"key":"ref_5","first-page":"300","article-title":"Two mutations within the coding sequence of the phenylalanine hydroxylase gene","volume":"85","author":"Svensson, E.; Andersson, B.; Hagenfeldt, L.","year":"1990","unstructured":"Svensson E, Andersson B, Hagenfeldt L. Two mutations within the coding sequence of the phenylalanine hydroxylase gene. Hum Genet 1990;85:300-4.","journal-title":"Hum Genet"},{"key":"ref_6","first-page":"38","article-title":"Two distinct mutations at a single BamHI site in phenylketonuria","volume":"28","author":"Melle, D.; Verelst, P.; Rey, F.; etal","year":"1991","unstructured":"Melle D, Verelst P, Rey F, etal. Two distinct mutations at a single BamHI site in phenylketonuria. J Med Genet 1991;28:38-40. R158Q P281L'3). Indeed, we found no muta-","journal-title":"J Med Genet; P281L'3). Indeed, we found no muta"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1093\/nar\/19.7.1427","article-title":"Application of natural and amplification are concerned, it is important to bear in mind created restriction sites for the diagnosis of PKU mutations","volume":"19","author":"Eiken, H.G.; Odland, E.; Boman, H.; Skjelkvale, L.; Engebretsen, L.F.; Apold, J.","year":"1991","unstructured":"Eiken HG, Odland E, Boman H, Skjelkvale L, Engebretsen LF, Apold J. Application of natural and amplification are concerned, it is important to bear in mind created restriction sites for the diagnosis of PKU mutations. Nucleic Acids Res 1991;19:1427-30.","journal-title":"Nucleic Acids Res"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/0888-7543(91)90225-4","article-title":"Phenylketonuria missense mutations in the Mediterranean","volume":"9","author":"Okano, Y.; Wang, T.; Eisensmith, R.C.","year":"1991","unstructured":"Okano Y, Wang T, Eisensmith RC, et al. Phenylketonuria missense mutations in the Mediterranean. Genomics 1991; 9:96-103.","journal-title":"Genomics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/327333a0","article-title":"An amino acid substitution involved in phenylketonuria is in linkage disequilibrium with DNA haplotype 2","volume":"327","author":"DiLella, A.G.; Marvit, J.; Brayton, K.; Woo, S.L.C.","year":"1987","unstructured":"DiLella AG, Marvit J, Brayton K, Woo SLC. An amino acid substitution involved in phenylketonuria is in linkage disequilibrium with DNA haplotype 2. Nature 1987; 327:333-6.","journal-title":"Nature"},{"key":"ref_10","first-page":"347","article-title":"A prevalent missense mutation in Northern In conclusion, the present study provides Europe associated with hyperphenylalaninaemia","volume":"150","author":"Okano, Y.; Eisensmith, R.C.; Dasovoch, M.; Wang, T.; Guttler, F.; Woo, S.L.C.","year":"1991","unstructured":"Okano Y, Eisensmith RC, Dasovoch M,Wang T, Guttler F, Woo SLC. A prevalent missense mutation in Northern In conclusion, the present study provides Europe associated with hyperphenylalaninaemia. Eur _7 Pediatr 1991;150:347-52."},{"key":"ref_11","first-page":"91","article-title":"Phenylketonuria in Poland: 66% of PKU zygotes for deleterious mutations in this alleles are caused by three mutations. Hum Genet geographical area accounts for the clinical","volume":"88","author":"Zygulska, M.; Eigel, A.; Dworniczak, B.; Sutkowska, A.; Pietrzyk, J.J.; Horst, J.","year":"1991","unstructured":"Zygulska M, Eigel A, Dworniczak B, Sutkowska A, Pietrzyk JJ, Horst J. Phenylketonuria in Poland: 66% of PKU zygotes for deleterious mutations in this alleles are caused by three mutations. Hum Genet geographical area accounts for the clinical 1991;88:91-4."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/BF00201832","article-title":"Spectrum of phenylketonuria mutations in Western Europe and North Africa, and their relation to polymorphic DNA haplotypes at the phenylalanine hydroxylase locus","volume":"86","author":"Berthelon, M.; Caillaud, C.; Rey, F.; etal","year":"1991","unstructured":"Berthelon M,Caillaud C, Rey F, etal. Spectrum of phenylketonuria mutations in Western Europe and North Africa, and their relation to polymorphic DNA haplotypes at the phenylalanine hydroxylase locus. Hum Genet 1991;86:355-8.","journal-title":"Hum Genet"},{"key":"ref_13","first-page":"377","article-title":"The phenylketonuria de la Recherche et de la Technologie. This locus: current knowledge about alleles and mutations of work was supported in part by a Polish grant the phenylalanine hydroxylase gene in various populations","volume":"87","author":"Konecki, D.S.; Lichter-Konecki, U.","year":"1991","unstructured":"Konecki DS, Lichter-Konecki U. The phenylketonuria de la Recherche et de la Technologie. This locus: current knowledge about alleles and mutations of work was supported in part by a Polish grant the phenylalanine hydroxylase gene in various populations. 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