Poster Presentation GENEMAPPERS 2026

SLC7A6OS founder variant is a rare cause of autosomal recessive progressive myoclonus epilepsy dated to 1,100 years ago (#94)

Bronwyn E Grinton 1 2 3 , Colin A Ellis 4 , Mered Parnes 5 6 , Laina Lusk 4 7 , Mariam Hull 5 , Krystal Skully 6 , Melanie Bahlo 2 3 , Samuel F Berkovic 1 , Gaetan Lesca 8 9 , Karen L Oliver 1 3
  1. Department of Medicine, The University of Melbourne, Heidelberg, VIC, Australia
  2. Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia
  3. Genetics and Gene Regulation Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Vic, Australia
  4. Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA
  5. Pediatric Movement Disorders Clinic, Texas Children's Hospital and Baylor College of Medicine, Houston, TX, USA
  6. Division of Neurology and Developmental Neurosciences, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA
  7. The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, USA
  8. Genetics Department, Lyon Civil Hospices, Lyon, France
  9. NeuroMyoGène Institute, University of Lyon, Claude Bernard University Lyon 1, Lyon, France

A homozygous variant, SLC7A6OS c.191A>G, was previously reported as a rare cause of progressive myoclonic epilepsy in two families from Portugal and Türkiye (1). A shared haplotype suggested the variant had been inherited from a common founder.

Three additional, unrelated probands with the same homozygous variant have recently been identified. The three new probands are of Puerto Rican ancestry, residing in the USA.  We studied all five families to determine whether the three new families shared the same ancestor as the original two families.

All homozygous variant carriers (n=9) presented with a progressive myoclonic epilepsy with onset between 9-21years. All patients experienced myoclonic seizures and ataxia.  Most patients also experienced tonic clonic seizures (n=6), cognitive decline (n=5) and were wheelchair-reliant (n=6). Early death was not observed; ages at last update range from 13-43 years.  

Haplotype analysis identified a shared 0.2 cM region (846kb) on chromosome 16q encompassing the SLC7A6OS variant consistent with the variant being inherited from a common ancestor. This region was defined by the Turkish family, which shared a smaller haplotype than the other four families. A haplotype spanning 3.1Mb was shared by the remaining families.

The most recent common ancestor of all five families was estimated to have lived 47 generations ago (95% CI: 19-68 generations), or ~1100 years. With the Turkish family excluded, the remaining four families are estimated to have shared a common ancestor 24 generations (95% CI: 9-66 generations) or ~600 years ago, whilst the three families from the USA are estimated to share a common ancestor 13 generation (95% CI: 3-60) or ~300 years ago. These timeframes are consistent with demographic events involving migration patterns between the Iberian Peninsula, Eastern Mediterranean region and Puerto Rico.

  1. 1) Mazzola L, Oliver KL, Labalme A, Baykan B, Muona M, Joensuu TH, et al. Progressive myoclonus epilepsy caused by a homozygous splicing variant of SLC7A6OS. Ann Neurol. 2021 Feb;89(2):402–7.