The Importance of Genetic Screening and Diagnostic Testing: A Case Study of a Phenylketonuria Family
Abstract
The present study aims to elucidate the genetic and molecular complexity of a family with previously diagnosed phenylketonuria (PKU), emphasising the importance of genetic screening and diagnostic testing in the management of inherited metabolic disorders. Following the initial biochemical diagnosis via newborn screening, a four-membered family (mother and three daughters from two different marriages) underwent molecular genetic testing. The DNA was extracted, and a Next Generation Sequencing (NGS) procedure was performed to analyse mutations in the phenylalanine hydroxylase (PAH) gene. Three daughters were the subjects of the evaluation: two were diagnosed with PKU and one was identified as a carrier. All affected individuals were compound heterozygotes with pathogenic variants in the PAH gene. The identified mutations were PAH (NM_000277.3): c.1208C>T (p.A403V), PAH (NM_000277.3): c.1243G>A (p.D415N) and PAH (NM_000277.3): c.688G>A (p.V230I), all previously reported in literature as pathogenic with mild to moderate phenotypic effects. One daughter exhibited normal development and was a heterozygous carrier. Despite delayed dietary compliance in the affected individuals, neurodevelopmental impairments were moderate, likely reflecting the genotype-phenotype correlations.Inherited metabolic diseases like PKU impose significant but preventable burdens on individuals and health systems. Pre-marital genetic counselling and targeted carrier screening, especially in populations with high consanguinity rates, are vital tools for prevention. Strengthening public awareness and genetic literacy can help cultivate a healthier generation through informed reproductive choices.
Keywords
Phenylketonuria, genetic diagnosis, next generation sequencing, compound heterozygous
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