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Brain somatic mutations are increasingly recognized as a major cause of focal epilepsies. These include mTOR pathway mutations underlying cortical malformations such as focal cortical dysplasia and hemimegalencephaly, and SLC35A2 mutations in MOGHE, and activating variants in the SHH pathway in hypothalamic hamartomas.
This study aims to identify brain somatic mutations using paired blood-brain samples and trace DNA from stereo-EEG electrodes, and to perform functional validation of candidate variants in children with drug-resistant focal epilepsy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Children undergoing epilepsy surgery at the Rothschild Foundation, Paris. | Sequencing of paired blood-brain DNA samples, SEEG electrodes |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sampling of blood, frozen resected tissues, and cerebrospinal fluid (CSF) | Genetic | Sampling of blood, frozen resected tissue, saliva, and cerebrospinal fluid (CSF); sequencing of paired blood-brain DNA samples, SEEG electrodes |
| Measure | Description | Time Frame |
|---|---|---|
| qualitative genetic analysis | Detection of brain somatic mutations and functional studies | baseline |
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Inclusion Criteria:
Exclusion Criteria:
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Children with focal drug-resistant epilepsy undergoing epilepsy surgery and their parents
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Amelie YAVCHITZ, MD | Contact | +33 1 48 03 64 54 | ayavchitz@for.paris | |
| Mathilde CHIPAUX, MD, PhD | Contact | +33 1 48 03 69 43 | mchipaux@for.paris |
| Name | Affiliation | Role |
|---|---|---|
| Mathilde CHIPAUX, MD, PhD | Fondation A de Rothschild | Principal Investigator |
| Stéphanie BAULAC, PhD | Institut du Cerveau | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fondation Ophtalmologique Adolphe de Rothschld | Recruiting | Paris | 75019 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31444548 | Result | Baldassari S, Ribierre T, Marsan E, Adle-Biassette H, Ferrand-Sorbets S, Bulteau C, Dorison N, Fohlen M, Polivka M, Weckhuysen S, Dorfmuller G, Chipaux M, Baulac S. Dissecting the genetic basis of focal cortical dysplasia: a large cohort study. Acta Neuropathol. 2019 Dec;138(6):885-900. doi: 10.1007/s00401-019-02061-5. Epub 2019 Aug 23. | |
| 33407896 |
| Label | URL |
|---|---|
| Related Info | View source |
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| ID | Term |
|---|---|
| D000092222 | Focal Cortical Dysplasia |
| D065705 | Hemimegalencephaly |
| D014402 | Tuberous Sclerosis |
| C537158 | Hypothalamic hamartomas |
| D004828 | Epilepsies, Partial |
| D004660 | Encephalitis |
| ID | Term |
|---|---|
| D065703 | Malformations of Cortical Development, Group I |
| D054220 | Malformations of Cortical Development |
| D009421 | Nervous System Malformations |
| D009422 | Nervous System Diseases |
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Cortical tissue removed during neurosurgical intervention for epilepsy, SEEG Electrodes, Blood, saliva and cerebrospinal fluid (CSF)
| Bonduelle T, Hartlieb T, Baldassari S, Sim NS, Kim SH, Kang HC, Kobow K, Coras R, Chipaux M, Dorfmuller G, Adle-Biassette H, Aronica E, Lee JH, Blumcke I, Baulac S. Frequent SLC35A2 brain mosaicism in mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE). Acta Neuropathol Commun. 2021 Jan 6;9(1):3. doi: 10.1186/s40478-020-01085-3. |
| 33434304 | Result | Lee WS, Baldassari S, Chipaux M, Adle-Biassette H, Stephenson SEM, Maixner W, Harvey AS, Lockhart PJ, Baulac S, Leventer RJ. Gradient of brain mosaic RHEB variants causes a continuum of cortical dysplasia. Ann Clin Transl Neurol. 2021 Feb;8(2):485-490. doi: 10.1002/acn3.51286. Epub 2021 Jan 12. |
| 33834539 | Result | Kim S, Baldassari S, Sim NS, Chipaux M, Dorfmuller G, Kim DS, Chang WS, Taly V, Lee JH, Baulac S. Detection of Brain Somatic Mutations in Cerebrospinal Fluid from Refractory Epilepsy Patients. Ann Neurol. 2021 Jun;89(6):1248-1252. doi: 10.1002/ana.26080. Epub 2021 Apr 20. |
| 36307217 | Result | Barba C, Blumcke I, Winawer MR, Hartlieb T, Kang HC, Grisotto L, Chipaux M, Bien CG, Hermanovska B, Porter BE, Lidov HGW, Cetica V, Woermann FG, Lopez-Rivera JA, Canoll PD, Mader I, D'Incerti L, Baldassari S, Yang E, Gaballa A, Vogel H, Straka B, Macconi L, Polster T, Grant GA, Krskova L, Shin HJ, Ko A, Crino PB, Krsek P, Lee JH, Lal D, Baulac S, Poduri A, Guerrini R; SLC35A2 Study Group. Clinical Features, Neuropathology, and Surgical Outcome in Patients With Refractory Epilepsy and Brain Somatic Variants in the SLC35A2 Gene. Neurology. 2023 Jan 31;100(5):e528-e542. doi: 10.1212/WNL.0000000000201471. Epub 2022 Oct 28. |
| 37324239 | Result | Checri R, Chipaux M, Ferrand-Sorbets S, Raffo E, Bulteau C, Rosenberg SD, Doladilhe M, Dorfmuller G, Adle-Biassette H, Baldassari S, Baulac S. Detection of brain somatic mutations in focal cortical dysplasia during epilepsy presurgical workup. Brain Commun. 2023 Jun 1;5(3):fcad174. doi: 10.1093/braincomms/fcad174. eCollection 2023. |
| 38710875 | Result | Ribierre T, Bacq A, Donneger F, Doladilhe M, Maletic M, Roussel D, Le Roux I, Chassoux F, Devaux B, Adle-Biassette H, Ferrand-Sorbets S, Dorfmuller G, Chipaux M, Baldassari S, Poncer JC, Baulac S. Targeting pathological cells with senolytic drugs reduces seizures in neurodevelopmental mTOR-related epilepsy. Nat Neurosci. 2024 Jun;27(6):1125-1136. doi: 10.1038/s41593-024-01634-2. Epub 2024 May 6. |
| 39460693 | Result | Sanders MWCB, Koeleman BPC, Brilstra EH, Jansen FE, Baldassari S, Chipaux M, Sim NS, Ko A, Kang HC, Blumcke I, Lal D, Baulac S, Lee JH, Aronica E, Braun KPJ. Somatic variant analysis of resected brain tissue in epilepsy surgery patients. Epilepsia. 2024 Dec;65(12):e209-e215. doi: 10.1111/epi.18148. Epub 2024 Oct 26. |
| 40307383 | Result | Baldassari S, Klingler E, Teijeiro LG, Doladilhe M, Raoux C, Roig-Puiggros S, Bizzotto S, Couturier J, Gilbert A, Sami L, Ribierre T, Aronica E, Adle-Biassette H, Chipaux M, Jabaudon D, Baulac S. Single-cell genotyping and transcriptomic profiling of mosaic focal cortical dysplasia. Nat Neurosci. 2025 May;28(5):964-972. doi: 10.1038/s41593-025-01936-z. Epub 2025 Apr 30. |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D058627 | Megalencephaly |
| D019465 | Craniofacial Abnormalities |
| D009139 | Musculoskeletal Abnormalities |
| D009140 | Musculoskeletal Diseases |
| D006222 | Hamartoma |
| D009369 | Neoplasms |
| D009378 | Neoplasms, Multiple Primary |
| D009386 | Neoplastic Syndromes, Hereditary |
| D020752 | Neurocutaneous Syndromes |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D030342 | Genetic Diseases, Inborn |
| D004827 | Epilepsy |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D000090862 | Neuroinflammatory Diseases |