2. Academic Validation
  3. Progressive Myoclonus Epilepsy Caused by a Homozygous Splicing Variant of SLC7A6OS

Progressive Myoclonus Epilepsy Caused by a Homozygous Splicing Variant of SLC7A6OS

  • Ann Neurol. 2021 Feb;89(2):402-407. doi: 10.1002/ana.25941.
Laure Mazzola 1 2,  Karen L Oliver 3 4 5,  Audrey Labalme 6,  Betül Baykan 7,  Mikko Muona 8 9,  Tarja H Joensuu 8 10,  Carolina Courage 8 10,  Nicolas Chatron 6 11,  Giuseppe Borsani 12,  Eudeline Alix 6,  Francis Ramond 13,  Renaud Touraine 13,  Melanie Bahlo 4 5,  Nerses Bebek 7,  Samuel F Berkovic 3,  Anna-Elina Lehesjoki 8 10,  Gaetan Lesca 6 11
Affiliations

Affiliations

  • 1 Neurology Department, Saint-Étienne University Hospital Center, Saint-Étienne, France.
  • 2 Lyon Neuroscience Research Center, Lyon, France.
  • 3 Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
  • 4 Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
  • 5 Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
  • 6 Genetics Department, Lyon Civil Hospices, Lyon, France.
  • 7 Departments of Neurology and Clinical Neurophysiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
  • 8 Folkhälsan Research Center, Helsinki, Finland.
  • 9 Blueprint Genetics, Helsinki, Finland.
  • 10 Medicum, University of Helsinki, Helsinki, Finland.
  • 11 NeuroMyoGène Institute, University of Lyon, Claude Bernard University Lyon 1, Lyon, France.
  • 12 University of Brescia, Brescia, Italy.
  • 13 Genetics Department, Saint-Étienne University Hospital Center, Saint-Étienne, France.
PMID: 33085104 DOI: 10.1002/ana.25941
Abstract

Exome Sequencing was performed in 2 unrelated families with progressive myoclonus epilepsy. Affected individuals from both families shared a rare, homozygous c.191A > G variant affecting a splice site in SLC7A6OS. Analysis of cDNA from lymphoblastoid cells demonstrated partial splice site abolition and the creation of an abnormal isoform. Quantitative Reverse Transcriptase polymerase chain reaction and Western blot showed a marked reduction of protein expression. Haplotype analysis identified a ~0.85cM shared genomic region on chromosome 16q encompassing the c.191A > G variant, consistent with a distant ancestor common to both families. Our results suggest that biallelic loss-of-function variants in SLC7A6OS are a novel genetic cause of progressive myoclonus epilepsy. ANN NEUROL 2021;89:402-407.

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