Mutations of the Phenylalanine Hydroxylase Gene in Thai Neonates with Suspected Phenylketonuria
Mutations of PAH Gene in Thai Neonates
Keywords:
Mutations, Phenylalanine hydroxylase gene, Phenylketonuria, Thai neonatesAbstract
Phenylketonuria (PKU) is a rare genetic disease caused by mutations of the phenylalanine hydroxylase (PAH) gene. This gene produces an enzyme, which metabolizes phenylalanine (Phe) into tyrosine (Tyr). Accumulation of Phe in the body leads to brain damage and mental retardation. To study PAH mutation in PKU-suspected Thai neonates, DNA extraction and sequencing were performed using leftover dried blood spot samples from the routine work of The Neonatal Screening Operating Centre. We selected 32 DBS which had confi rmed Phe in serum > 2.3 mg/dL and Phe/Tyr ratio > 2 (n = 32). The sequencing results showed all samples had 2–5 point mutations. From the total of 17 mutation types; 13 were missense mutations, 3 were silence mutations and 1 was a mutation at regulatory element. Especially, missense mutations were found in 17 samples (53.12%) with Phe in serum > 5 mg/dL. Due to the limitation of Sanger sequencing and many point mutations found, Next Generation Sequencing (NGS) may be used for targeted gene sequencing to diagnose PKU effectively.
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