Journal of Molecular Medicine

, Volume 91, Issue 12, pp 1399–1406 | Cite as

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

  • Jose Felix Martí-MassóEmail author
  • Alberto Bergareche
  • Vladimir Makarov
  • Javier Ruiz-Martinez
  • Ana Gorostidi
  • Adolfo López de Munain
  • Juan Jose Poza
  • Pasquale Striano
  • Joseph D. Buxbaum
  • Coro Paisán-RuizEmail author
Original Article


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.


FCMTE Whole exome sequencing ACMSD Kynurenine Pathway 



We thank the patients and their families for participating in this study. This work is supported in part by the “Instituto de Salud Carlos III” (FIS PI10/02714; JFMM) and the National Institute of Neurological Disorders and Stroke of the National Institute of Health under award number R21NS082881 to CPR.

Conflict of interest

All authors declare they have no competing interest.

Supplementary material

109_2013_1075_MOESM1_ESM.pdf (56 kb)
ESM 1 (PDF 56 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Jose Felix Martí-Massó
    • 1
    • 2
    • 3
    • 4
    • 12
    Email author
  • Alberto Bergareche
    • 1
    • 2
    • 3
  • Vladimir Makarov
    • 5
  • Javier Ruiz-Martinez
    • 1
    • 2
    • 3
  • Ana Gorostidi
    • 1
    • 2
    • 3
  • Adolfo López de Munain
    • 1
    • 2
    • 3
    • 4
  • Juan Jose Poza
    • 1
    • 2
    • 3
  • Pasquale Striano
    • 6
  • Joseph D. Buxbaum
    • 7
    • 8
    • 9
    • 10
  • Coro Paisán-Ruiz
    • 7
    • 8
    • 10
    • 11
    Email author
  1. 1.Biodonostia Research Institute, Neurosciences areaUniversity of the Basque Country, EHU-UPVSan SebastianSpain
  2. 2.Hospital Universitario Donostia, Department of Neurology, Movement Disorders UnitSan SebastianSpain
  3. 3.Centro de investigación biomédica en Red para enfermedades Neurodegenerativas (CIBERNED), Carlos III Health InstituteMadridSpain
  4. 4.Department of NeurosciencesUniversity of the Basque Country, EHU-UPVSan SebastianSpain
  5. 5.Department of BiostatisticsColumbia University, Mailman School of Public HealthNew YorkUSA
  6. 6.Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences-DINOGMI, Gaslini InstituteGenoaItaly
  7. 7.Department of PsychiatryIcahn School of Medicine at Mount SinaiNew YorkUSA
  8. 8.Department of Genetics and Genomic SciencesIcahn School of Medicine at Mount SinaiNew YorkUSA
  9. 9.Department of NeurosciencesIcahn School of Medicine at Mount SinaiNew YorkUSA
  10. 10.Friedman Brain and Mindich Child Health and Development Institutes, Icahn School of Medicine at Mount SinaiNew YorkUSA
  11. 11.Department of NeurologyIcahn School of Medicine at Mount SinaiNew YorkUSA
  12. 12.Department of Neurology, Hospital DonostiaSan SebastianSpain

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