An intriguing "silent" mutation and a founder effect in antiquitin (ALDH7A1).

Abstract

Recently, alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase deficiency was shown to cause pyridoxine-dependent epilepsy in a considerable number of patients. alpha-AASA dehydrogenase deficiency is an autosomal recessive disorder characterized by a neonatal-onset epileptic encephalopathy in which seizures are resistant to antiepileptic drugs but respond immediately to the administration of pyridoxine (OMIM 266100). Increased plasma and urinary levels of alpha-AASA are associated with pathogenic mutations in the alpha-AASA dehydrogenase (ALDH7A1/antiquitin) gene. Here, we report an intriguing "silent" mutation in ALDH7A1, a novel missense mutation and a founder mutation in a Dutch cohort (10 patients) with alpha-AASA dehydrogenase deficiency.