Title | Severe infantile onset developmental and epileptic encephalopathy caused by mutations in autophagy gene WDR45 |
Authors | Carvill, Gemma L. Liu, Aijie Mandelstam, Simone Schneider, Amy Lacroix, Amy Zemel, Matthew McMahon, Jacinta M. Bello-Espinosa, Luis Mackay, Mark Wallace, Geoffrey Waak, Michaela Zhang, Jing Yang, Xiaoling Malone, Stephen Zhang, Yue-Hua Mefford, Heather C. Scheffer, Ingrid E. |
Affiliation | Northwestern Univ, Feinberg Sch Med, Ken & Ruth Davee Dept Neurol, Chicago, IL 60611 USA. Peking Univ, Hosp 1, Dept Pediat, Beijing, Peoples R China. Florey Inst Neurosci & Mental Hlth, Parkville, Vic, Australia. Univ Melbourne, Royal Childrens Hosp, Dept Paediat, Melbourne, Vic, Australia. Univ Melbourne, Royal Childrens Hosp, Dept Radiol, Melbourne, Vic, Australia. Univ Melbourne, Epilepsy Res Ctr, Dept Med, Austin Hlth, Heidelberg, Vic, Australia. Univ Washington, Dept Pediat, Div Genet Med, Seattle, WA 98195 USA. Univ Calgary, Alberta Childrens Hosp, Dept Paediat, Calgary, AB, Canada. Lady Cilento Childrens Hosp, Dept Neurol, Brisbane, Qld, Australia. Peking Univ, Hosp 1, Dept Pediat, Beijing, Peoples R China. Scheffer, IE (reprint author), Florey Inst Neurosci & Mental Hlth, Parkville, Vic, Australia. Mefford, HC (reprint author), Univ Washington, Dept Pediat, Div Genet Med, Seattle, WA 98195 USA. |
Keywords | de novo variant genetics magnetic resonance imaging DEE PROTEIN-ASSOCIATED NEURODEGENERATION BRAIN IRON ACCUMULATION DE-NOVO MUTATIONS CHILDHOOD |
Issue Date | 2018 |
Publisher | EPILEPSIA |
Citation | EPILEPSIA. 2018, 59(1), E5-E13. |
Abstract | Heterozygous de novo variants in the autophagy gene, WDR45, are found in beta-propeller protein-associated neurodegeneration (BPAN). BPAN is characterized by adolescent onset dementia and dystonia; 66% patients have seizures. We asked whether WDR45 was associated with developmental and epileptic encephalopathy (DEE). We performed next generation sequencing of WDR45 in 655 patients with developmental and epileptic encephalopathies. We identified 3/655 patients with DEE plus 4 additional patients with de novo WDR45 pathogenic variants (6 truncations, 1 missense); all were female. Six presented with DEE and 1 with early onset focal seizures and profound regression. Median seizure onset was 12 months, 6 had multiple seizure types, and 5/7 had focal seizures. Three patients had magnetic resonance susceptibility-weighted imaging; blooming was noted in the globus pallidi and substantia nigra in the 2 older children aged 4 and 9 years, consistent with iron accumulation. We show that de novo pathogenic variants are associated with a range of developmental and epileptic encephalopathies with profound developmental consequences. |
URI | http://hdl.handle.net/20.500.11897/500133 |
ISSN | 0013-9580 |
DOI | 10.1111/epi.13957 |
Indexed | SCI(E) PubMed |
Appears in Collections: | 第一医院 |