BACKGROUND: Early-onset epileptic encephalopathy (EOEE) is a heterogeneous group of neurodevelopmental disorders characterised by infantile-onset intractable epilepsy and unfavourable developmental outcomes. Hundreds of mutations have been reported to cause EOEE; however, little is known about the clinical features of individuals with rare variants. CASE REPORT AND METHODS: We present a 10-year-old boy with severe developmental delay. He started experiencing recurrent focal seizures at 2 months old. Serial electroencephalograms persistently detected epileptiform discharges from the left hemisphere. Whole-exome sequencing and array-comparative genome hybridization were performed to search for de novo variations. Two-week-old C57Bl/6 mice were used for immunofluorescence studies. RESULTS: This case had a paternally inherited, 0.2-Mb duplication at chromosome 22q11.22. The whole-exome sequencing identified a de novo truncating mutation of tripartite motif containing 8 (TRIM8) (NM_030912:c.1099_1100insG:p.C367fs), one of the epileptic encephalopathy-associated genes. We verified that the murine homologues of these genes are expressed in the postnatal mouse brain. CONCLUSION: This is the second case of EOEE caused by a de novo truncating mutation of TRIM8. Further studies are required to determine the functional roles of TRIM8 in the postnatal development of the human brain and its functional relationships with other EOEE-associated genes.
BACKGROUND: Early-onset epilepticencephalopathy (EOEE) is a heterogeneous group of neurodevelopmental disorders characterised by infantile-onset intractable epilepsy and unfavourable developmental outcomes. Hundreds of mutations have been reported to cause EOEE; however, little is known about the clinical features of individuals with rare variants. CASE REPORT AND METHODS: We present a 10-year-old boy with severe developmental delay. He started experiencing recurrent focal seizures at 2 months old. Serial electroencephalograms persistently detected epileptiform discharges from the left hemisphere. Whole-exome sequencing and array-comparative genome hybridization were performed to search for de novo variations. Two-week-old C57Bl/6 mice were used for immunofluorescence studies. RESULTS: This case had a paternally inherited, 0.2-Mb duplication at chromosome 22q11.22. The whole-exome sequencing identified a de novo truncating mutation of tripartite motif containing 8 (TRIM8) (NM_030912:c.1099_1100insG:p.C367fs), one of the epilepticencephalopathy-associated genes. We verified that the murine homologues of these genes are expressed in the postnatal mouse brain. CONCLUSION: This is the second case of EOEE caused by a de novo truncating mutation of TRIM8. Further studies are required to determine the functional roles of TRIM8 in the postnatal development of the human brain and its functional relationships with other EOEE-associated genes.
Authors: Nuria C Bramswig; O Caluseriu; H-J Lüdecke; F V Bolduc; N C L Noel; T Wieland; H M Surowy; H-J Christen; H Engels; T M Strom; D Wieczorek Journal: Hum Genet Date: 2017-01-25 Impact factor: 4.132
Authors: Patricia L Weng; Amar J Majmundar; Kamal Khan; Tze Y Lim; Shirlee Shril; Gina Jin; John Musgrove; Minxian Wang; Dina F Ahram; Vimla S Aggarwal; Louise E Bier; Erin L Heinzen; Ana C Onuchic-Whitford; Nina Mann; Florian Buerger; Ronen Schneider; Konstantin Deutsch; Thomas M Kitzler; Verena Klämbt; Amy Kolb; Youying Mao; Christelle Moufawad El Achkar; Adele Mitrotti; Jeremiah Martino; Bodo B Beck; Janine Altmüller; Marcus R Benz; Shoji Yano; Mohamad A Mikati; Talha Gunduz; Heidi Cope; Vandana Shashi; Howard Trachtman; Monica Bodria; Gianluca Caridi; Isabella Pisani; Enrico Fiaccadori; Asmaa S AbuMaziad; Julian A Martinez-Agosto; Ora Yadin; Jonathan Zuckerman; Arang Kim; Ulrike John-Kroegel; Amanda V Tyndall; Jillian S Parboosingh; A Micheil Innes; Agnieszka Bierzynska; Ania B Koziell; Mordi Muorah; Moin A Saleem; Julia Hoefele; Korbinian M Riedhammer; Ali G Gharavi; Vaidehi Jobanputra; Emma Pierce-Hoffman; Eleanor G Seaby; Anne O'Donnell-Luria; Heidi L Rehm; Shrikant Mane; Vivette D D'Agati; Martin R Pollak; Gian Marco Ghiggeri; Richard P Lifton; David B Goldstein; Erica E Davis; Friedhelm Hildebrandt; Simone Sanna-Cherchi Journal: Am J Hum Genet Date: 2021-01-27 Impact factor: 11.025
Authors: S Polani; M Dean; A Lichter-Peled; S Hendrickson; S Tsang; X Fang; Y Feng; W Qiao; G Avni; G Kahila Bar-Gal Journal: J Genet Mutat Disord Date: 2022-01