Molecular Characteristics, Phenotypic Diversity and Genotype-Estimated Therapeutic Responsiveness of Serbian Patients with Phenylketonuria / MOLEKULARNE KARAKTERISTIKE, FENOTIPSKA RAZNOLIKOST I PROCENA ODGOVORA NA TERAPIJU ZASNOVANA NA GENOTIPU KOD SRPSKIH PACIJENATA SA FENILKETONURIJOM
| Autor: | Sonja Pavlovic, Kristel Klaassen, Maja Stojiljkovic-Petrovic |
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| Rok vydání: | 2014 |
| Předmět: |
Genetics
congenital hereditary and neonatal diseases and abnormalities education.field_of_study Mutation Phenylalanine hydroxylase biology Biochemistry (medical) Clinical Biochemistry Population nutritional and metabolic diseases Phenylalanine medicine.disease_cause Phenotype Complementation Genotype biology.protein medicine education Gene |
| Zdroj: | Journal of Medical Biochemistry. 33:97-107 |
| ISSN: | 1452-8266 1452-8258 |
| DOI: | 10.2478/jomb-2013-0031 |
| Popis: | Summary Phenylketonuria (PKU) is a rare, inherited metabolic disease which is transmitted in an autosomal recessive pattern. PKU is caused by mutations in the gene encoding the phenylalanine hydroxylase (PAH) enzyme. This review cites the most prominent methods for the detection of mutations in the PAH gene. Since the image of PKU transcends »simple« monogenic disease, the known data on non-coding PAH gene variants and their role and PKU modifier genes have been further reviewed. It has been shown that there is a significant correlation between mutant PAH genotypes and PKU phenotypes. However, genotype-phenotype correlation inconsistencies have also been found. This review discusses the possible causes of phenotypic inconsistencies, such as oversight of more than two mutations present in the patient’s PAH genotype, pitfalls of patient phenotypic classification (plasma phenylalanine concentration and phenylalanine tolerance), the inter-allelic complementation (positive and negative) phenomenon. A new therapeutic approach, tetrahydrobiopterin (BH4) supplementation therapy, is an important innovation in the course of PKU patients’ treatment. How - ever, in countries where the BH4-loading test and BH4-supplementation therapy are not available, a genotype-based estimation of responsiveness to the therapy is a valuable approach. It enables BH4-potential benefit estimation, which provides vital information both for the patient and for the population. An optimal molecular diagnostics algorithm, established according to the published mutation frequencies in Serbian PKU patients, has been suggested. In the future, the molecular-genetic algorithm for PKU could be expanded to include a variety of transcriptional regulatory elements located in noncoding PAH gene regions and yet to be discovered modifier genes. |
| Databáze: | OpenAIRE |
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