Detection of Somatic Mutations in Sporadic Epilepsies

Improving genetic diagnostic yield in familial and sporadic cerebral cavernous malformations: detection of copy number and deep Intronic variants

N Sikta, S Gooley, TE Green, O Hoeper, T Witkowski, C Bennett, D Francis, J Reid, K Mao, M Awad, S Roberts-Thomson, K Bulluss, J Clark, IE Scheffer, P Perucca, MF Bennett, M Bahlo, SF Berkovic, MS Hildebrand

2025-08-01

Cerebral cavernous malformations (CCMs) are intracranial vascular lesions associated with risk of haemorrhages and seizures. While..

Cell-type-informed genotyping of mosaic focal epilepsies reveals cell-autonomous and non-cell-autonomous disease-associated transcriptional programs

S Bizzotto, M Talukdar, EA Stronge, RB Ramirez, Y Yang, AY Huang, Q Hu, Y Hou, NK Hylton, B Finander, A Tillett, Z Zhou, BH Chhouk, AM D’Gama, E Yang, TE Green, DC Reutens, SA Mullen, IE Scheffer, MS Hildebrand

2025-07-22

While it is widely accepted that somatic variants that activate the PI3K-mTOR pathway are a major cause of drug-resistant focal ep..

PAK3 pathogenic variant associated with sleep-related hypermotor epilepsy in a family with parental mosaicism

A Gambardella, YC Liu, MF Bennett, TE Green, JA Damiano, F Fortunato, MJ Coleman, J Cherfils, JV Barnier, J Gecz, M Bahlo, SF Berkovic, MS Hildebrand

2025-04-01

Protein-activated kinases mediate spine morphogenesis and synaptic plasticity. PAK3 is part of the p21-activated kinases (PAKs) fa..

Experience of the first adult-focussed undiagnosed disease program in Australia (AHA-UDP): solving rare and puzzling genetic disorders is ageless

M Wallis, SD Bodek, J Munro, H Rafehi, MF Bennett, Z Ye, A Schneider, F Gardiner, G Valente, E Murdoch, E Uebergang, J Hunter, C Stutterd, A Huq, L Salmon, I Scheffer, D Eratne, S Meyn, CY Fong, T John

2024-12-01

Background: Significant recent efforts have facilitated increased access to clinical genetics assessment and genomic sequencing fo..

Are Germline Mosaic TSC1/2 Variants Present in Controls? Implications for Diagnosis

Z Ye, S Lin, X Zhao, M Wallis, X Gao, L Sun, J Wu, J Duan, Y Yao, L Li, L Chen, D Cao, Z Hu, VW Zhang, SF Berkovic, IE Scheffer, J Liao, MS Hildebrand

2024-01-01

Contribution of Somatic Ras/Raf/Mitogen-Activated Protein Kinase Variants in the Hippocampus in Drug-Resistant Mesial Temporal Lobe Epilepsy

S Khoshkhoo, Y Wang, Y Chahine, EZ Erson-Omay, SM Robert, E Kiziltug, EC Damisah, C Nelson-Williams, G Zhu, W Kong, AY Huang, E Stronge, HW Phillips, BH Chhouk, S Bizzotto, MH Chen, TN Adikari, Z Ye, T Witkowski, D Lai

2023-06-12

Importance: Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy subtype and is often refractory to antiseizure ..

Mosaicism in tuberous sclerosis complex: Lowering the threshold for clinical reporting

Z Ye, S Lin, X Zhao, MF Bennett, NJ Brown, M Wallis, X Gao, L Sun, J Wu, R Vedururu, T Witkowski, F Gardiner, C Stutterd, J Duan, SA Mullen, G McGillivray, S Bodek, G Valente, M Reagan, Y Yao

2022-12-01

Tuberous sclerosis complex (TSC) is a multi-system genetic disorder. Most patients have germline mutations in TSC1 or TSC2 but, 10..

Sporadic hypothalamic hamartoma is a ciliopathy with somatic and bi-allelic contributions

TE Green, JE Motelow, MF Bennett, Z Ye, CA Bennett, NG Griffin, JA Damiano, RJ Leventer, JL Freeman, AS Harvey, PJ Lockhart, LG Sadleir, A Boys, IE Scheffer, H Major, BW Darbro, M Bahlo, DB Goldstein, JF Kerrigan, EL Heinzen

2022-07-15

Hypothalamic hamartoma with gelastic seizures is a well-established cause of drug-resistant epilepsy in early life. The developmen..

Evidence for a Dual-Pathway, 2-Hit Genetic Model for Focal Cortical Dysplasia and Epilepsy

MF Bennett, MS Hildebrand, S Kayumi, MA Corbett, S Gupta, Z Ye, M Krivanek, R Burgess, OJ Henry, JA Damiano, A Boys, J Gécz, M Bahlo, IE Scheffer, SF Berkovic

2022-02-25

Background and ObjectivesThe 2-hit model of genetic disease is well established in cancer, yet has only recently been reported to ..

Somatic IDH1 variant (p.R132C) in an adult male with Maffucci syndrome

NJ Brown, Z Ye, C Stutterd, SI Jayasinghe, A Schneider, S Mullen, SA Mandelstam, MS Hildebrand

2021-12-01

Maffucci syndrome is a rare, highly variable somatic mosaic condition, and well-known cancer-related gain-of-function variants in ..

Improving Specificity of Cerebrospinal Fluid Liquid Biopsy for Genetic Testing

Z Ye, IE Scheffer, SF Berkovic, MS Hildebrand

2021-10-01

Cerebrospinal fluid liquid biopsy for detecting somatic mosaicism in brain

Z Ye, Z Chatterton, J Pflueger, JA Damiano, L McQuillan, AS Harvey, S Malone, H Do, W Maixner, A Schneider, B Nolan, M Wood, WS Lee, G Gillies, K Pope, M Wilson, PJ Lockhart, A Dobrovic, IE Scheffer, M Bahlo

2021-01-01

Brain somatic mutations are an increasingly recognized cause of epilepsy, brain malformations and autism spectrum disorders and ma..

Familial adult myoclonic epilepsy type 1 SAMD12 TTTCA repeat expansion arose 17,000 years ago and is present in Sri Lankan and Indian families

MF Bennett, KL Oliver, BM Regan, ST Bellows, AL Schneider, H Rafehi, N Sikta, DE Crompton, M Coleman, MS Hildebrand, MA Corbett, T Kroes, J Gecz, IE Scheffer, SF Berkovic, M Bahlo

2020-07-01

Familial adult myoclonic epilepsy 1 (FAME1), first recognised in Japanese families, was recently shown to be caused by a TTTCA rep..

SCN1A Variants in vaccine-related febrile seizures: A prospective study

JA Damiano, L Deng, W Li, R Burgess, AL Schneider, NW Crawford, J Buttery, M Gold, P Richmond, KK Macartney, MS Hildebrand, IE Scheffer, N Wood, SF Berkovic

2020-02-01

Objective: Febrile seizures may follow vaccination. Common variants in the sodium channel gene, SCN1A, are associated with febrile..

Somatic GNAQ mutation in the forme fruste of Sturge-Weber syndrome

MS Hildebrand, AS Harvey, S Malone, JA Damiano, H Do, Z Ye, L McQuillan, W Maixner, R Kalnins, B Nolan, M Wood, E Ozturk, NC Jones, G Gillies, K Pope, PJ Lockhart, A Dobrovic, RJ Leventer, IE Scheffer, SF Berkovic

2018-06-01

Objective To determine whether the GNAQ R183Q mutation is present in the forme fruste cases of Sturge-Weber syndrome (SWS) to esta..

Sensitive quantitative detection of somatic mosaic mutation in “double cortex” syndrome

JA Damiano, H Do, E Ozturk, R Burgess, R Kalnins, NC Jones, A Dobrovic, SF Berkovic, MS Hildebrand

2017-12-01

Aims. Somatic mutation of the lissencephaly-1 gene is a cause of subcortical band heterotopia (“double cortex”). The severity of t..