Katalin Štěrbová1, Markéta Vlčková2, Petr Klement3, Jana Neupauerová4, David Staněk4, Hana Zůnová2, Pavel Seeman4, Petra Laššuthová4. 1. Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic. 2. Department of Biology and Medical Genetics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic. 3. Department of Neurology, General University Hospital, Prague, Czech Republic. 4. DNA Laboratory, Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic.
Abstract
BACKGROUND: Recently, a study providing insight into GABRB3 mutational spectrum was published (Møller et al 2017). The authors report considerable pleiotropy even for single mutations and were not able to identify any genotype-phenotype correlations. METHODS: The proband (twin B) was referred for massively parallel sequencing of epilepsy-related gene panel because of hypotonia and neonatal seizures. The revealed variant was confirmed with Sanger sequencing in the proband and the twin A, and both parents were tested for the presence of the variant. RESULTS: We report a case of epilepsy of infancy with migrating focal seizures (EIMFS) of neonatal onset in monozygotic twins with a de novo novel GABRB3 variant p.Thr281Ala. The variant has a uniform presentation on an identical genomic background. In addition, early seizure-onset epilepsy associated with GABRB3 mutation has been until now described only for the p.Leu256Gln variant in the GABRB3 (Møller et al 2017, Myers et al 2016) located in the transmembrane domain just as the p.Thr281Ala variant described here. CONCLUSION: De novo GABRB3 mutations may cause neonatal-onset EIMFS with early-onset hypotonia, respiratory distress, and severe developmental delay. Georg Thieme Verlag KG Stuttgart · New York.
BACKGROUND: Recently, a study providing insight into GABRB3 mutational spectrum was published (Møller et al 2017). The authors report considerable pleiotropy even for single mutations and were not able to identify any genotype-phenotype correlations. METHODS: The proband (twin B) was referred for massively parallel sequencing of epilepsy-related gene panel because of hypotonia and neonatal seizures. The revealed variant was confirmed with Sanger sequencing in the proband and the twin A, and both parents were tested for the presence of the variant. RESULTS: We report a case of epilepsy of infancy with migrating focal seizures (EIMFS) of neonatal onset in monozygotic twins with a de novo novel GABRB3 variant p.Thr281Ala. The variant has a uniform presentation on an identical genomic background. In addition, early seizure-onset epilepsy associated with GABRB3 mutation has been until now described only for the p.Leu256Gln variant in the GABRB3 (Møller et al 2017, Myers et al 2016) located in the transmembrane domain just as the p.Thr281Ala variant described here. CONCLUSION: De novo GABRB3 mutations may cause neonatal-onset EIMFS with early-onset hypotonia, respiratory distress, and severe developmental delay. Georg Thieme Verlag KG Stuttgart · New York.
Authors: Tiong Yang Tan; Jiří Sedmík; Mark P Fitzgerald; Rivka Sukenik Halevy; Liam P Keegan; Ingo Helbig; Lina Basel-Salmon; Lior Cohen; Rachel Straussberg; Wendy K Chung; Mayada Helal; Reza Maroofian; Henry Houlden; Jane Juusola; Simon Sadedin; Lynn Pais; Katherine B Howell; Susan M White; John Christodoulou; Mary A O'Connell Journal: Am J Hum Genet Date: 2020-03-26 Impact factor: 11.025