Abstract
The rare autosomal recessive disorder pyridoxine 5'-phosphate oxidase (PNPO) deficiency is a recently described cause of neonatal and infantile seizures. Clinical evaluation, and biochemical and genetic testing, were performed on a neonate with intractable seizures who did not respond to anticonvulsant drugs and pyridoxine. Sequencing of the PNPO gene revealed a novel homozygous c.284G>A transition in exon 3, resulting in arginine to histidine substitution and reduced activity of the PNPO mutant to 18% relative to the wild type. This finding enabled molecular prenatal diagnosis in a subsequent pregnancy, accurate genetic counseling in the large inbred family, and population screening.
MeSH terms
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Amino Acid Substitution
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Animals
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Brain Diseases, Metabolic, Inborn / diagnosis
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Brain Diseases, Metabolic, Inborn / enzymology*
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Brain Diseases, Metabolic, Inborn / genetics
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Brain Diseases, Metabolic, Inborn / metabolism*
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CHO Cells
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Codon, Nonsense
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Consanguinity
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Cricetinae
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Cricetulus
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DNA Mutational Analysis
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Exons
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Female
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Gene Expression
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Genetic Testing
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Humans
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Infant, Newborn
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Male
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Mutagenesis, Site-Directed
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Pedigree
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Point Mutation
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Prenatal Diagnosis
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Pyridoxaminephosphate Oxidase / deficiency*
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Pyridoxaminephosphate Oxidase / genetics
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Pyridoxine / metabolism*
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Seizures / diagnosis
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Seizures / enzymology
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Seizures / genetics
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Seizures / metabolism
Substances
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Codon, Nonsense
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Pyridoxaminephosphate Oxidase
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Pyridoxine