An intriguing “silent” mutation and a founder effect in antiquitin (ALDH7A1)



Recently, α-aminoadipic semialdehyde (α-AASA) dehydrogenase deficiency was shown to cause pyridoxine-dependent epilepsy in a considerable number of patients. α-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 α-AASA are associated with pathogenic mutations in the α-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 α-AASA dehydrogenase deficiency. Ann Neurol 2007