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Human Genetics

, Volume 132, Issue 3, pp 275–283 | Cite as

Identification of COL6A2 mutations in progressive myoclonus epilepsy syndrome

  • Siamak Karkheiran
  • Catharine E. Krebs
  • Vladimir Makarov
  • Yalda Nilipour
  • Benjamin Hubert
  • Hossein Darvish
  • Steven Frucht
  • Gholam Ali Shahidi
  • Joseph D. Buxbaum
  • Coro Paisán-RuizEmail author
Original Investigation

Abstract

In this study, a consanguineous family with progressive myoclonus epilepsy (PME) was clinically examined and molecularly investigated to determine the molecular events causing disease. Since exclusion of known genes indicated that novel genes causing PME still remained unidentified, homozygosity mapping, exome sequencing, as well as validation and disease-segregation analyses were subsequently carried out for both loci and gene identification. To further assure our results, a muscle biopsy and gene expression analyses were additionally performed. As a result, a homozygous, disease-segregating COL6A2 mutation, p.Asp215Asn, absent in a large number of control individuals, including control individuals of Iranian ancestry, was identified in both affected siblings. COL6A2 was shown to be expressed in the human cerebral cortex and muscle biopsy revealed no specific histochemical pathology. We conclude that the COL6A2 p.Asp215Asn mutation is likely to be responsible for PME in this family; however, additional studies are warranted to further establish the pathogenic role of both COL6A2 and the extracellular proteolysis system in the pathogenesis of PME.

Keywords

Muscular Dystrophy Exome Sequencing Piracetam Human Cerebral Cortex Congenital Muscular Dystrophy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The authors would like to thank the patients and their relatives for their participation in this study. The authors also thank the Department of Neurology and the Friedman Brain Institute at the Mount Sinai School of Medicine for support (C.P-R).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

439_2012_1248_MOESM1_ESM.tif (577 kb)
Supplementary material 1 (TIFF 577 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Siamak Karkheiran
    • 1
  • Catharine E. Krebs
    • 2
  • Vladimir Makarov
    • 3
    • 4
  • Yalda Nilipour
    • 5
  • Benjamin Hubert
    • 2
  • Hossein Darvish
    • 6
  • Steven Frucht
    • 2
    • 7
  • Gholam Ali Shahidi
    • 1
    • 8
  • Joseph D. Buxbaum
    • 3
    • 4
    • 7
    • 9
    • 10
  • Coro Paisán-Ruiz
    • 2
    • 4
    • 7
    • 10
    Email author
  1. 1.Movement Disorders Clinic, Hazrat Rasool HospitalTehran University of Medical SciencesTehranIran
  2. 2.Department of NeurologyMount Sinai School of MedicineNew YorkUSA
  3. 3.The Seaver Autism Center for Research and TreatmentMount Sinai School of MedicineNew YorkUSA
  4. 4.Department of PsychiatryMount Sinai School of MedicineNew YorkUSA
  5. 5.Department of Pathology, Myopathology LabToos HospitalTehranIran
  6. 6.Department of Clinical GeneticsShahid Beheshti University of Medical SciencesTehranIran
  7. 7.Friedman Brain InstituteMount Sinai School of MedicineNew YorkUSA
  8. 8.Department of Neurology, Hazrat Rasool HospitalTehran University of Medical SciencesTehranIran
  9. 9.Department of NeuroscienceMount Sinai School of MedicineNew YorkUSA
  10. 10.Department of Genetics and Genomic SciencesMount Sinai School of MedicineNew YorkUSA

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