Mutation analysis of the PAH gene in phenylketonuria patients from Rio de Janeiro, Southeast Brazil

Molecular Genetics & Genomic Medicine
Eduardo Vieira NetoMárcia G Ribeiro

Abstract

Phenylketonuria (PKU) is an autosomal recessive disease resulting from mutations in the PAH gene. Most of the patients are compound heterozygotes, and genotype is a major factor in determining the phenotypic variability of PKU. More than 1,000 variants have been described in the PAH gene. Rio de Janeiro's population has a predominance of Iberian, followed by African and Amerindian ancestries. It is expected that most PKU variants in this Brazilian state have originated in the Iberian Peninsula. However, rare European, African or pathogenic variants that are characteristic of the admixed population of the state might also be found. A total of 102 patients were included in this study. Genomic DNA was isolated from dried blood spots. Sanger sequencing was used for PAH gene variant identification. Deletions and duplications were also screened using MLPA analysis. Haplotypes were also determined. Nine (8.8%) homozygous and 93 (91.2%) compound heterozygous patients were found. The spectrum included 37 causative mutations. Missense, nonsense, and splicing pathogenic variants corresponded to 63.7%, 2.9%, and 22.6% of the mutant alleles, respectively. Large (1.5%), and small deletions, inframe (5.4%) and with frameshift (3.9%), comprise...Continue Reading

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Citations

Feb 20, 2020·Revista paulista de pediatria : orgão oficial da Sociedade de Pediatria de São Paulo·Roseli Divino CostaMarcial Francis Galera
Nov 10, 2020·Scandinavian Journal of Clinical and Laboratory Investigation·Zhendong ZhaoChaohui Fu
Jan 20, 2021·Molecular Genetics & Genomic Medicine·Filipa FerreiraLaura Vilarinho

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Methods Mentioned

BETA
gel filtration
PCR
Exome Sequencing

Software Mentioned

Poly
‐ 2
MutationTaster
SIFT
Provean
Phen
Ensembl
Mutation Taster
PolyPhen
GeneMapper

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