Mutations in antiquitin in individuals with pyridoxine-dependent seizures

  title={Mutations in antiquitin in individuals with pyridoxine-dependent seizures},
  author={Philippa B Mills and Eduard A. Struys and Cornelis Jakobs and Barbara Plecko and Peter Baxter and Matthias R. Baumgartner and Mich{\`e}l A.A.P. Willemsen and Heymut Omran and Uta Tacke and Birgit Uhlenberg and Bernhard Weschke and Peter T. Clayton},
  journal={Nature Medicine},
We show here that children with pyridoxine-dependent seizures (PDS) have mutations in the ALDH7A1 gene, which encodes antiquitin; these mutations abolish the activity of antiquitin as a Δ1-piperideine-6-carboxylate (P6C)–α-aminoadipic semialdehyde (α-AASA) dehydrogenase. The accumulating P6C inactivates pyridoxal 5′-phosphate (PLP) by forming a Knoevenagel condensation product. Measurement of urinary α-AASA provides a simple way of confirming the diagnosis of PDS and ALDH7A1 gene analysis… 
Pyridoxine-dependent epilepsy: A novel mutation in a Tunisian child.
Two novel ALDH7A1 (antiquitin) splicing mutations associated with pyridoxine‐dependent seizures
Two unrelated patients affected with PDS are reported as a result of α‐aminoadipic semialdehyde (α‐AASA) dehydrogenase deficiency caused by pathogenic ALDH7A1/antiquitin mutations, which are novel and result in erroneous splicing as showed by messenger RNA (mRNA) studies.
Pyridoxine responsive epilepsy caused by a novel homozygous PNPO mutation☆
Novel mutations in pyridoxine-dependent epilepsy.
  • A. MilletG. Salomons S. Hamelin
  • Medicine, Biology
    European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society
  • 2011
An intriguing “silent” mutation and a founder effect in antiquitin (ALDH7A1)
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 are reported.
Atypical pyridoxine-dependent epilepsy due to a pseudoexon in ALDH7A1.
Clinical, biochemical, and molecular studies in pyridoxine‐dependent epilepsy. Antisense therapy as possible new therapeutic option
The aim of this work was the clinical, biochemical, and genetic analysis of 12 unrelated patients, mostly from Spain, in an attempt to provide further valuable data regarding the wide clinical, genetic, and biochemical spectrum of the disease.
Glial localization of antiquitin: Implications for pyridoxine‐dependent epilepsy
Tissue from a child with PDE as well as control human and murine brain is analyzed to determine the normal distribution of antiquitin, its distribution in PDE, and associated brain malformations.
First cases of pyridoxine-dependent epilepsy in Bulgaria: novel mutation in the ALDH7A1 gene
The first genetically proven cases of PDE in Bulgaria are reported, both clinically and electrographically, to large daily supplements of pyridoxine (vitamin B6).


A gene for pyridoxine-dependent epilepsy maps to chromosome 5q31.
A recombination event in one family defined the distal boundary of the genetic interval encompassing the PDE gene (5.1 cM), and ongoing studies may lead to the identification of the disease-causing gene.
Pyridoxal Phosphate De-activation by Pyrroline-5-carboxylic Acid
Pyrroline-5-carboxylic acid is found to be a unique endogenous vitamin antagonist, which may contribute to seizures in hyperprolinemia type II, but they may be preventable with long term vitamin B6supplementation.
Pipecolic acid elevation in plasma and cerebrospinal fluid of two patients with pyridoxine‐dependent epilepsy
Two patients with pyridoxine‐dependent epilepsy with significant elevation of pipecolic acid concentrations in plasma and cerebrospinal fluid (CSF) and further increase of pipeColic acid in CSF during a 72‐hour pyridine withdrawal are reported on.
Pyridoxal phosphate is better than pyridoxine for controlling idiopathic intractable epilepsy
PLP could replace PN in the treatment of intractable childhood epilepsy, particularly inThe treatment of infantile spasms, and within six months of treatment with PLP or PN, five of the 11 patients were seizure free and had their previous antiepileptic medicine tapered off gradually.
Pyridoxine dependent epilepsy: a suggestive electroclinical pattern
There is an identifiable EEG pattern that is highly suggestive of pyridoxine dependent epilepsy that is probably under diagnosed and used to improve the chances of early diagnosis.
The pcd Gene Encoding Piperideine-6-Carboxylate Dehydrogenase Involved in Biosynthesis of α-Aminoadipic Acid Is Located in the Cephamycin Cluster ofStreptomyces clavuligerus
Three open reading frames (ORFs) have been located downstream of cefE in the cephamycin C gene cluster of Streptomyces clavuligerus and encodes a high molecular weight penicillin-binding protein.
Differences in the roles of conserved glutamic acid residues in the active site of human class 3 and class 2 aldehyde dehydrogenases
  • C. J. MannH. Weiner
  • Biology, Chemistry
    Protein science : a publication of the Protein Society
  • 1999
The data suggest that even though the subunit structures and active site residues of the isozymes are similar, the enzymes have very distinct properties besides their oligomeric state (dimer vs. tetramer) and substrate specificity.