Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients
J. inborn errors metab. screen
; 7: e20190012, 2019. tab
Artigo
em Inglês
|
LILACS-Express
| LILACS
| ID: biblio-1090982
Biblioteca responsável:
BR1.1
ABSTRACT
Abstract Phenylketonuria (PKU, OMIM 261600) is predominantly caused by mutations in the PAH gene. One hundred and three Argentine PKU 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 in exon 7 (26%), 12 (12%), 11 (10%), and 6 (10%). 77% were missense, and 77% affected the enzyme catalytic domain, nine mutations accounted for 57% of 179 studied alleles p.Arg261Gln (Allele frequency(AF)10.6%), c.1066-11G>A (AF9,5%), p.Arg408Trp (AF8,3%), p.Tyr414Cys (AF5,5%), p.Ala403Val, p.Val388Met, and p.Arg158Gln (AF 5% each), p.Leu48Ser, and p.Ile65Thr (AF4% each). The predicted phenotype was assigned by Guldberg´s arbitrary value (AV) and compared with the clinical phenotype based in tolerance to Phe intake. 29.1% (n30) were hyperphenylalaninemias, 18.5% (n19) mild-PKU, 27.2% (n28) moderate-PKU and 25.2 % (n26) classical-PKU. Genotype/phenotype correlation was statistically significant (p<0.001) Overall concordance was 62,5% 93.3% in hyperphenylalaninemia, 64.7% in mild-PKU and 65.4% in classical patients. The moderate-PKU showed a weak concordance (17%) with milder AV prediction than clinical assessment. 74% of discordant moderate patients harbored p.Arg261Gln, and p.Val388Met. Our cohort is highly heterogeneous, with predominant Mediterranean influence (mainly Spanish), but with differences with other Latin-American countries.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
LILACS
País/Região como assunto:
América do Sul
/
Argentina
Idioma:
Inglês
Revista:
J. inborn errors metab. screen
Assunto da revista:
Medicina Cl¡nica
/
Patologia
Ano de publicação:
2019
Tipo de documento:
Artigo
País de afiliação:
Argentina
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Espanha
Instituição/País de afiliação:
Fundación de Endocrinología Infantil (FEI)/AR
/
Hospital de Niños "Sor Ludovica"/AR
/
Universidad Autónoma de Madrid/ES