Compound Heterozygous ALDH7A1 Mutation Causes the Hemi-Allelic Expression in a Patient with Pyridoxine-Dependent Epilepsy

Abstract

Pyridoxine-dependent epilepsy (PDE) is an inherited disease with an autosomal recessive trait caused by deficiency of α-amino-adipic semialdehyde (AASA) dehydrogenase encoded by the ALDH7A1 gene. Pyridoxine administration is usually effective for the treatment of PDE. We identified compound heterozygous ALDH7A1 mutation in a patient with undiagnosed intractable epilepsy. One of the mutations was located in the splicing region of this gene. We analyzed the RNA expression patterns and confirmed the hemi-allelic expression of this gene, which could be considered a consequence of erroneous splicing, though this was not direct evidence of a splicing error. The severe developmental delay observed in this patient could have been avoidable by prompt treatment intervention in the early neonatal period. Therefore, it is important to remind that vitamin B6 should be prescribed for neonatal patients with clustering seizures occurring soon after birth.

Keywords

• rna splicing
• hemi-allelic expression
• neonatal seizure
• damaging scores
• reverse transcribed-pcr