Loss-of-Function Mutations in <i>FRRS1L</i> Lead to an Epileptic-Dyskinetic Encephalopathy

Madeo M., Stewart M., Sun Y., Sahir N., Wiethoff S., Chandrasekar I., ...Daha Fazla

AMERICAN JOURNAL OF HUMAN GENETICS, cilt.98, sa.6, ss.1249-1255, 2016 (SCI-Expanded) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 98 Sayı: 6
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1016/j.ajhg.2016.04.008
  • Dergi Adı: AMERICAN JOURNAL OF HUMAN GENETICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1249-1255
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Hayır

Özet

Glutamatergic neurotransmission governs excitatory signaling in the mammalian brain, and abnormalities of glutamate signaling have been shown to contribute to both epilepsy and hyperkinetic movement disorders. The etiology of many severe childhood movement disorders and epilepsies remains uncharacterized. We describe a neurological disorder with epilepsy and prominent choreoathetosis caused by biallelic pathogenic variants in FRRS1L, which encodes an AMPA receptor outer-core protein. Loss of FRRS1L function attenuates AMPA-mediated currents, implicating chronic abnormalities of glutamatergic neurotransmission in this monogenic neurological disease of childhood.