Linkage disequilibrium between phenylketonuria and RFLP haplotype 1 at the phenylalanine hydroxylase locus in Portugal |
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Authors: | Catherine Caillaud Laura Vilarinho Antoine Vilarinho Françoise Rev Monique Bertheion Rosario Santos Stanislas Lyonnet Marie-Louise Briard Rui Vaz Osorio Jean Rev Arnold Munnich |
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Affiliation: | (1) Unité de Recherches sur les Handicaps Génétiques de l'Enfant INSERM U-12, Hôpital des Enfants-Malades, 149, Rue de Sèvres, F-75743, 15 Paris Cedex, France;(2) Instituto de Genetica Medica Jacinto de Magalhaes, Praça Pedro Nunes 74, P-4000 Porto, Portugal |
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Abstract: | Summary RFLPs of 36 normal and 41 mutant alleles at the phenylalanine hydroxylase locus were determined in 31 Portuguese kindreds. A total of 14 haplotypes including 10 normal and 7 mutant alleles were observed. Almost 75% of all mutant alleles were confined within only two haplotypes, namely haplotype 9 (17.1%) and haplotype 1 (56.1%). This frequency of mutant haplotype 1 in Portugal is, to our knowledge, the highest for this mutant haplotype in all studies reported to date. Other mutant haplotypes were either rare (haplotype 2, 9.7%) or totally absent (haplotype 3, 0%). Only 24.5% of all mutant alleles were found to consistently carry identified mutations, particularly R261Q (9.8%), R252W (3.3%), R408W (1.6%) and I94 (3.3%). A new mutation, L249F, located in the seventh exon of the gene, accounted for 6.5% of all mutant alleles in our series. Interestingly, this mutant genotype was consistently associated with mutant haplotype 1 (P<0.01), as also observed for the R261Q mutation. It appears, therefore, that mutant haplotype 1 is genotypically heterogeneous in Portugal and that more than two mutations account for its prevalence in this country. |
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