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Two novel ALDH7A1 (antiquitin) splicing mutations associated with pyridoxine‐dependent seizures
Author(s) -
Striano Pasquale,
Battaglia Silvia,
Giordano Lucio,
Capovilla Giuseppe,
Beccaria Francesca,
Struys Eduard A.,
Salomons Gajja S.,
Jakobs Cornelis
Publication year - 2009
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2008.01741.x
Subject(s) - pyridoxine , medicine , exon , alternative splicing , gene , bioinformatics , pharmacology , genetics , biology
Summary Pyridoxine‐dependent seizures (PDS) is a rare autosomal recessive disorder causing intractable seizures in neonates and infants. Patients are typically resistant to conventional anticonvulsants but respond well to the administration of pyridoxine. We report two unrelated patients affected with PDS as a result of α‐aminoadipic semialdehyde (α‐AASA) dehydrogenase deficiency caused by pathogenic ALDH7A1 /antiquitin mutations. Two of the three reported mutations are novel and result in erroneous splicing, as showed by messenger RNA (mRNA) studies. So far, the vast majority of the patients clinically diagnosed as PDS show α‐AASA dehydrogenase deficiency, caused by mutations in the ALDH7A1 gene. However, despite the availability of reliable biomarkers, early consideration of a pyridoxine trial is still the most important issue in a child with therapy‐resistant seizures.