Mutation and haplotype analysis of phenylalanine hydroxylase alleles in classical PKU patients from the Czech Republic: identification of four novel mutations
Language English Country Great Britain, England Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
9391881
PubMed Central
PMC1051115
DOI
10.1136/jmg.34.11.893
Knihovny.cz E-resources
- MeSH
- Alleles * MeSH
- Phenylalanine Hydroxylase genetics MeSH
- Phenylketonurias enzymology genetics MeSH
- Genetic Markers MeSH
- Genotype MeSH
- Haplotypes MeSH
- Humans MeSH
- Mutation * MeSH
- DNA Mutational Analysis MeSH
- Polymorphism, Genetic MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- Phenylalanine Hydroxylase MeSH
- Genetic Markers MeSH
Mutations, haplotypes, and other polymorphic markers in the phenylalanine hydroxylase (PAH) gene were analysed in 133 unrelated Czech families with classical phenylketonuria (PKU). Almost 95% of all mutant alleles were identified, using a combination of PCR and restriction analysis, denaturing gradient gel electrophoresis (DGGE), and sequencing. A total of 30 different mutations, 16 various RFLP/VNTR haplotypes, and four polymorphisms were detected on 266 independent mutant chromosomes. The most common molecular defect observed in the Czech population was R408W (54.9%). Each of the other 29 mutations was present in no more than 5% of alleles and 13 mutations were found in only one PKU allele each (0.4%). Four novel mutations G239A, R270fsdel5bp, A342P, and IVS11nt-8g-->a were identified. In 14 (5.1%) alleles, linked to four different RFLP/VNTR haplotypes, the sequence alterations still remain unknown. Our results confirm that PKU is a heterogeneous disorder at the molecular level. Since there is evidence for the gene flow coming from northern, western, and southern parts of Europe into our Slavic population, it is clear that human migration has been the most important factor in the spread of PKU alleles in Europe.
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Hum Genet. 1994 Sep;94(3):307-10 PubMed
Nat Genet. 1994 Jun;7(2):169-75 PubMed
Am J Hum Genet. 1994 Oct;55(4):851-3 PubMed
Hum Genet. 1994 Nov;94(5):573-5 PubMed
Am J Hum Genet. 1995 Jan;56(1):278-86 PubMed
Hum Mol Genet. 1994 Sep;3(9):1675-7 PubMed
Hum Mutat. 1994;4(4):297-9 PubMed
Am J Hum Genet. 1995 May;56(5):1034-41 PubMed
Acta Paediatr Suppl. 1994 Dec;407:19-26 PubMed
Am J Hum Genet. 1995 Aug;57(2):201-23 PubMed
Hum Genet. 1995 Oct;96(4):472-6 PubMed
Hum Mutat. 1995;6(2):192-4 PubMed
Eur J Hum Genet. 1995;3(4):246-55 PubMed
Nucleic Acids Res. 1996 Jan 1;24(1):127-31 PubMed
Hum Mutat. 1996;8(1):19-22 PubMed
Am J Hum Genet. 1985 Jul;37(4):619-34 PubMed
Acta Paediatr Scand Suppl. 1980;280:1-80 PubMed
Nucleic Acids Res. 1989 Jul 11;17(13):4937-46 PubMed
Nucleic Acids Res. 1991 Apr 25;19(8):1958 PubMed
Nucleic Acids Res. 1991 Apr 25;19(8):1959 PubMed
Genomics. 1991 Jun;10(2):449-56 PubMed
J Med Genet. 1991 Oct;28(10):686-90 PubMed
Genomics. 1991 Oct;11(2):242-6 PubMed
Nucleic Acids Res. 1992 Feb 25;20(4):927 PubMed
Am J Hum Genet. 1992 Sep;51(3):627-36 PubMed
Am J Hum Genet. 1992 Dec;51(6):1355-65 PubMed
J Med Genet. 1993 Feb;30(2):129-30 PubMed
Nucleic Acids Res. 1993 May 11;21(9):2261-2 PubMed
Hum Mol Genet. 1993 May;2(5):577-81 PubMed
Genomics. 1993 Jul;17(1):141-6 PubMed
J Biol Chem. 1994 Mar 25;269(12):9137-46 PubMed
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