Phenylalanine hydroxylase deficiency in Mexico: genotype-phenotype correlations, BH4 responsiveness and evidence of a founder effect

作者：Vela Amieva M; Abreu Gonzalez M; Gonzalez del Angel A; Ibarra Gonzalez I; Fernandez Lainez C; Barrientos Rios R; Monroy Santoyo S; Guillen Lopez S; Alcantara Ortigoza M A^*

来源：Clinical Genetics, 2015, 88(1): 62-67.

DOI：10.1111/cge.12444

• hyperphenylalaninemia
• phenylketonuria
• PKU
• tetrahydrobiopterin

The mutational spectrum of the phenylalanine hydroxylase gene (PAH) in Mexico is unknown, although it has been suggested that PKU variants could have a differential geographical distribution. Genotype-phenotype correlations and genotype-based predictions of responsiveness to tetrahydrobiopterin (BH4) have never been performed. We sequenced the PAH gene and determined the geographic origin of each allele, mini-haplotype associated, genotype-phenotype correlations and genotype-based prediction of BH4 responsiveness in 48 Mexican patients. The mutational spectrum included 34 variants with c.60+5G>T being the most frequent (20.8%) and linked to haplotype 4.3 possibly because of a founder effect and/or genetic drift. Two new variants were found c.1A>T and c.969+6T>C. The genotype-phenotype correlation was concordant in 70.8%. The genotype-based prediction to BH4-responsiveness was 41.7%, this information could be useful for the rational selection of candidates for BH4 testing and therapy.

• 出版日期2015-7