Phenylketonuria in Portugal: Genotype-Phenotype Correlations Using Molecular, Biochemical, and Haplotypic Analyses
| Autor: | Francisco Silva, Sónia Ramos, Helena Fonseca, Luísa Azevedo, Filipa Ferreira, Raquel Neiva, Carmen Sousa, Ana Marcão, Laura Vilarinho, Paula Garcia, Patrícia Janeiro, Sílvia Sequeira, Esmeralda Martins, António Amorim, Esmeralda Rodrigues, Luísa Diogo, Anabela Bandeira, Hugo Rocha, Ana C. Ferreira, Ana Maria Minarelli Gaspar, Teresa Campos, Célia Carmona, Luísa C. Rodrigues |
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| Přispěvatelé: | Instituto de Investigação e Inovação em Saúde |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Phenylalanine hydroxylase HDE MTB biochemical and genetic findings Population phenylketonuria Phenylalanine Disease QH426-470 030105 genetics & heredity Biology Compound heterozygosity Biochemical 03 medical and health sciences Portuguese population Neonatal Screening Gene Frequency Liver enzyme Phenylketonurias Genetics Humans Phenylketonuria Haplotypic Study Mutation Spectrum education Molecular Biology Genotype-Phenotype Correlations Genetics (clinical) haplotypic study education.field_of_study Portugal Homozygote Infant Newborn Phenylalanine Hydroxylase Original Articles Biochemical and genetic findings 030104 developmental biology Phenotype Haplotypes Genetic marker Mutation biology.protein mutation spectrum Genetic Findings Female Original Article |
| Zdroj: | Molecular Genetics & Genomic Medicine Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) Agência para a Sociedade do Conhecimento (UMIC)-FCT-Sociedade da Informação instacron:RCAAP Molecular Genetics & Genomic Medicine, Vol 9, Iss 3, Pp n/a-n/a (2021) |
| Popis: | Background The impairment of the hepatic enzyme phenylalanine hydroxylase (PAH) causes elevation of phenylalanine levels in blood and other body fluids resulting in the most common inborn error of amino acid metabolism (phenylketonuria). Persistently high levels of phenylalanine lead to irreversible damage to the nervous system. Therefore, early diagnosis of the affected individuals is important, as it can prevent clinical manifestations of the disease. Methods In this report, the biochemical and genetic findings performed in 223 patients diagnosed through the Portuguese Neonatal Screening Program (PNSP) are presented. Results Overall, the results show that a high overlap exists between different types of variants and phenylalanine levels. Molecular analyses reveal a wide mutational spectrum in our population with a total of 56 previously reported variants, most of them found in compound heterozygosity (74% of the patients). Intragenic polymorphic markers were used to assess the haplotypic structure of mutated chromosomes for the most frequent variants found in homozygosity in our population (p.Ile65Thr, p.Arg158Gln, p.Leu249Phe, p.Arg261Gln, p.Val388Met, and c.1066‐11G>A). Conclusion Our data reveal high heterogeneity at the biochemical and molecular levels and are expected to provide a better understanding of the molecular basis of this disease and to provide clues to elucidate genotype–phenotype correlations. The present study identify and characterize the variants underlying PKU in affected individuals in the Portuguese PKU/HPA cohort. Biochemical data, haplotic analysis and genetic findings performed in 223 patients diagnosed through the Portuguese Neonatal Screening Program (PNSP) is presented. The information obtained will improve the diagnostic applicability of mutational analysis and the capacity to predict the evolution of the disease. |
| Databáze: | OpenAIRE |
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