Phenylketonuria Diagnosis by Massive Parallel Sequencing and Genotype-Phenotype Association in Brazilian Patients.
Genes (Basel)
; 12(1)2020 12 25.
Article
in En
| MEDLINE
| ID: mdl-33375644
ABSTRACT
Phenylketonuria (PKU) is a common inborn error of amino acid metabolism in which the enzyme phenylalanine hydroxylase, which converts phenylalanine to tyrosine, is functionally impaired due to pathogenic variants in the PAH gene. Thirty-four Brazilian patients with a biochemical diagnosis of PKU, from 33 unrelated families, were analyzed through next-generation sequencing in the Ion Torrent PGM™ platform. Phenotype-genotype correlations were made based on the BioPKU database. Three patients required additional Sanger sequencing analyses. Twenty-six different pathogenic variants were identified. The most frequent variants were c.1315+1G>A (n = 8/66), c.473G>A (n = 6/66), and c.1162G>A (n = 6/66). One novel variant, c.524C>G (p.Pro175Arg), was found in one allele and was predicted as likely pathogenic by the American College of Medical Genetics and Genomics (ACMG) criteria. The molecular modeling of p.Pro175Arg indicated that this substitution can affect monomers binding in the PAH tetramer, which could lead to a change in the stability and activity of this enzyme. Next-generation sequencing was a fast and effective method for diagnosing PKU and is useful for patient phenotype prediction and genetic counseling.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phenylalanine Hydroxylase
/
Phenylketonurias
/
Genetic Testing
Type of study:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
/
Newborn
Country/Region as subject:
America do sul
/
Brasil
Language:
En
Journal:
Genes (Basel)
Year:
2020
Document type:
Article
Affiliation country: