The ACMSD gene, involved in tryptophan metabolism, is mutated in a family with cortical myoclonus, epilepsy, and parkinsonism

Jose Felix Martí-Massó, Alberto Bergareche, Vladimir Makarov, Javier Ruiz-Martinez, Ana Gorostidi, Adolfo López De Munain, Juan Jose Poza, Pasquale Striano, Joseph D. Buxbaum, Coro Paisán-Ruiz

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Familial cortical myoclonic tremor and epilepsy is a phenotypically and genetically heterogeneous autosomal dominant disorder characterized by the presence of cortical myoclonic tremor and epilepsy that is often accompanied by additional neurological features. Despite the numerous familial studies performed and the number of loci identified, there is no gene associated with this syndrome. It is expected that through the application of novel genomic technologies, such as whole exome sequencing and whole genome sequencing, a substantial number of novel genes will come to light in the coming years. In this study, we describe the identification of two disease-segregating mutations in a large family featuring cortical myoclonic tremor with epilepsy and parkinsonism. Due to the previous association of ACMSD deficiency with the development of epileptic seizures, we concluded that the identified nonsense mutation in the ACMSD gene, which encodes for a critical enzyme of the kynurenine pathway of the tryptophan metabolism, is the disease-segregating mutation most likely to be responsible for the phenotype described in our family. This finding not only reveals the identification of the first gene associated with familial cortical myoclonic tremor and epilepsy but also discloses the kynurenine pathway as a potential therapeutic target for the treatment of this devastating syndrome. Key message: ACMSD is mutated in a family with cortical myoclonus, epilepsy, and parkinsonism. ACMSD mutation contributes to the development of FCMTE QA accumulation is likely to play an important role in the pathogenesis of FCMTE. The kynurenine pathway as a potential drug target for the treatment of epilepsy.

Original languageEnglish
Pages (from-to)1399-1406
Number of pages8
JournalJournal of Molecular Medicine
Volume91
Issue number12
DOIs
Publication statusPublished - Dec 2013

Fingerprint

Myoclonic Epilepsy
Parkinsonian Disorders
Kynurenine
Tryptophan
Epilepsy
Tremor
Mutation
Genes
Exome
Nonsense Codon
Therapeutics
Genome
Technology
Phenotype
Enzymes
Pharmaceutical Preparations
Epilepsy, Myoclonic, Benign Adult Familial, Type 1

Keywords

  • ACMSD
  • FCMTE
  • Kynurenine Pathway
  • Whole exome sequencing

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

Cite this

Martí-Massó, J. F., Bergareche, A., Makarov, V., Ruiz-Martinez, J., Gorostidi, A., De Munain, A. L., ... Paisán-Ruiz, C. (2013). The ACMSD gene, involved in tryptophan metabolism, is mutated in a family with cortical myoclonus, epilepsy, and parkinsonism. Journal of Molecular Medicine, 91(12), 1399-1406. https://doi.org/10.1007/s00109-013-1075-4

The ACMSD gene, involved in tryptophan metabolism, is mutated in a family with cortical myoclonus, epilepsy, and parkinsonism. / Martí-Massó, Jose Felix; Bergareche, Alberto; Makarov, Vladimir; Ruiz-Martinez, Javier; Gorostidi, Ana; De Munain, Adolfo López; Poza, Juan Jose; Striano, Pasquale; Buxbaum, Joseph D.; Paisán-Ruiz, Coro.

In: Journal of Molecular Medicine, Vol. 91, No. 12, 12.2013, p. 1399-1406.

Research output: Contribution to journalArticle

Martí-Massó, JF, Bergareche, A, Makarov, V, Ruiz-Martinez, J, Gorostidi, A, De Munain, AL, Poza, JJ, Striano, P, Buxbaum, JD & Paisán-Ruiz, C 2013, 'The ACMSD gene, involved in tryptophan metabolism, is mutated in a family with cortical myoclonus, epilepsy, and parkinsonism', Journal of Molecular Medicine, vol. 91, no. 12, pp. 1399-1406. https://doi.org/10.1007/s00109-013-1075-4
Martí-Massó, Jose Felix ; Bergareche, Alberto ; Makarov, Vladimir ; Ruiz-Martinez, Javier ; Gorostidi, Ana ; De Munain, Adolfo López ; Poza, Juan Jose ; Striano, Pasquale ; Buxbaum, Joseph D. ; Paisán-Ruiz, Coro. / The ACMSD gene, involved in tryptophan metabolism, is mutated in a family with cortical myoclonus, epilepsy, and parkinsonism. In: Journal of Molecular Medicine. 2013 ; Vol. 91, No. 12. pp. 1399-1406.
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AU - De Munain, Adolfo López

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