Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients

MIÑANA, MARIANA NUÑEZ; SALERNO, MERCEDES; PRIETO, LAURA; CHIESA, ANA ELENA; ENACÁN, ROSA E.; VALLE, MARIA GABRIELA; FERNANDEZ, LUIS; SANTOS-SIMARRO, FERNANDO; FRAGA, CLAUDIA I.; SPECOLA, NORMA; LAPUNZINA, PABLO

Journal of Inborn Errors of Metabolism and Screening

Scielo

Lugar: Porto Alegre; Año: 2019 vol. 7 p. 1 - 8

Phenylketonuria (PKU, OMIM 261600) is predominantly caused by mutations in the PAH gene. One hundred and three ArgentinePKU patients were studied by Sanger sequencing; 101 were completely characterized (90.3% were compound heterozygotes).Fifty-four different pathogenic variants were identified. Mutations were distributed all along the PAH gene but concentrated inexon 7 (26%), 12 (12%), 11 (10%), and 6 (10%). 77% were missense, and 77% affected the enzyme catalytic domain, nine mutationsaccounted for 57% of 179 studied alleles: p.Arg261Gln (Allele frequency(AF):10.6%), c.1066-11G>A (AF:9,5%), p.Arg408Trp (AF:8,3%),p.Tyr414Cys (AF:5,5%), p.Ala403Val, p.Val388Met, and p.Arg158Gln (AF: 5% each), p.Leu48Ser, and p.Ile65Thr (AF:4% each). Thepredicted phenotype was assigned by Guldberg´s arbitrary value (AV) and compared with the clinical phenotype based in toleranceto Phe intake. 29.1% (n:30) were hyperphenylalaninemias, 18.5% (n:19) mild-PKU, 27.2% (n:28) moderate-PKU and 25.2 % (n:26)classical-PKU. Genotype/phenotype correlation was statistically significant (p