Genetic Insights Into Hypothalamic Hamartoma: Unraveling Somatic Variants.

Journal

Neurology. Genetics
ISSN: 2376-7839
Titre abrégé: Neurol Genet
Pays: United States
ID NLM: 101671068

Informations de publication

Date de publication:
Oct 2024
Historique:
received: 17 04 2024
accepted: 12 06 2024
medline: 9 9 2024
pubmed: 9 9 2024
entrez: 9 9 2024
Statut: epublish

Résumé

Hypothalamic hamartomas (HHs) are rare developmental brain lesions associated with drug-resistant epilepsy and often subjected to epilepsy surgery. Brain somatic variants in genes affecting the Sonic hedgehog (Shh) and primary cilia signaling pathways have been implicated in approximately 50% of nonsyndromic HH cases. This study aims to characterize a new cohort of 9 HH cases and elucidate their genetic etiology. We recruited 9 HH cases including 8 nonsyndromic cases of which 4 were type IV HH. Genomic DNA was extracted from peripheral blood and surgical brain tissues, and somatic variants were investigated using high-depth whole-exome sequencing. Pathogenic somatic variants in known HH genes ( Our findings reinforce the role of somatic variants in Shh and cilia genes in HH cases while also shedding light on

Identifiants

DOI: 10.1212/NXG.0000000000200180 PMID: 39246740 PMC: PMC11380500
pubmed: 39246740
doi: 10.1212/NXG.0000000000200180
pii: NXG-2024-100105
pmc: PMC11380500
doi:

Types de publication

Journal Article

Langues

eng

Pagination

e200180

Informations de copyright

Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Déclaration de conflit d'intérêts

The authors report no relevant disclosures. Go to Neurology.org/NG for full disclosures.

Auteurs

Lina Sami (L)

From the Institut du Cerveau-Paris Brain Institute-ICM (L.S., M.D., J.-M.D.S.A., E.L., Sara Baldassari, Stephanie Baulac), Sorbonne Université, Inserm, CNRS, Hôpital de la Pitié Salpêtrière; Department of Pediatric Neurosurgery (M.C., S.F.-S., C.B., E.R., S.R., G.D., R.C.), Rothschild Foundation Hospital EPICARE; Department of Medical Genetics (J.-M.D.S.A., E.L.), AP-HP, Sorbonne Université, Hôpital de la Pitié Salpêtrière; and Université de Paris Cité (H.A.-B.), service d'Anatomie Pathologique, AP-HP, Hôpital Lariboisière, DMU DREAM, Biobank BB-0033-00064, UMR 1141, INSERM, Paris, France.
ORCID: 0009-0002-8422-8186

Mathilde Chipaux (M)

From the Institut du Cerveau-Paris Brain Institute-ICM (L.S., M.D., J.-M.D.S.A., E.L., Sara Baldassari, Stephanie Baulac), Sorbonne Université, Inserm, CNRS, Hôpital de la Pitié Salpêtrière; Department of Pediatric Neurosurgery (M.C., S.F.-S., C.B., E.R., S.R., G.D., R.C.), Rothschild Foundation Hospital EPICARE; Department of Medical Genetics (J.-M.D.S.A., E.L.), AP-HP, Sorbonne Université, Hôpital de la Pitié Salpêtrière; and Université de Paris Cité (H.A.-B.), service d'Anatomie Pathologique, AP-HP, Hôpital Lariboisière, DMU DREAM, Biobank BB-0033-00064, UMR 1141, INSERM, Paris, France.
ORCID: 0000-0002-8454-7374

Sarah Ferrand-Sorbets (S)

From the Institut du Cerveau-Paris Brain Institute-ICM (L.S., M.D., J.-M.D.S.A., E.L., Sara Baldassari, Stephanie Baulac), Sorbonne Université, Inserm, CNRS, Hôpital de la Pitié Salpêtrière; Department of Pediatric Neurosurgery (M.C., S.F.-S., C.B., E.R., S.R., G.D., R.C.), Rothschild Foundation Hospital EPICARE; Department of Medical Genetics (J.-M.D.S.A., E.L.), AP-HP, Sorbonne Université, Hôpital de la Pitié Salpêtrière; and Université de Paris Cité (H.A.-B.), service d'Anatomie Pathologique, AP-HP, Hôpital Lariboisière, DMU DREAM, Biobank BB-0033-00064, UMR 1141, INSERM, Paris, France.
ORCID: 0009-0005-1841-0571

Marion Doladilhe (M)

From the Institut du Cerveau-Paris Brain Institute-ICM (L.S., M.D., J.-M.D.S.A., E.L., Sara Baldassari, Stephanie Baulac), Sorbonne Université, Inserm, CNRS, Hôpital de la Pitié Salpêtrière; Department of Pediatric Neurosurgery (M.C., S.F.-S., C.B., E.R., S.R., G.D., R.C.), Rothschild Foundation Hospital EPICARE; Department of Medical Genetics (J.-M.D.S.A., E.L.), AP-HP, Sorbonne Université, Hôpital de la Pitié Salpêtrière; and Université de Paris Cité (H.A.-B.), service d'Anatomie Pathologique, AP-HP, Hôpital Lariboisière, DMU DREAM, Biobank BB-0033-00064, UMR 1141, INSERM, Paris, France.
ORCID: 0009-0000-7502-9850

Christine Bulteau (C)

From the Institut du Cerveau-Paris Brain Institute-ICM (L.S., M.D., J.-M.D.S.A., E.L., Sara Baldassari, Stephanie Baulac), Sorbonne Université, Inserm, CNRS, Hôpital de la Pitié Salpêtrière; Department of Pediatric Neurosurgery (M.C., S.F.-S., C.B., E.R., S.R., G.D., R.C.), Rothschild Foundation Hospital EPICARE; Department of Medical Genetics (J.-M.D.S.A., E.L.), AP-HP, Sorbonne Université, Hôpital de la Pitié Salpêtrière; and Université de Paris Cité (H.A.-B.), service d'Anatomie Pathologique, AP-HP, Hôpital Lariboisière, DMU DREAM, Biobank BB-0033-00064, UMR 1141, INSERM, Paris, France.
ORCID: 0009-0005-5984-9310

Emmanuel Raffo (E)

From the Institut du Cerveau-Paris Brain Institute-ICM (L.S., M.D., J.-M.D.S.A., E.L., Sara Baldassari, Stephanie Baulac), Sorbonne Université, Inserm, CNRS, Hôpital de la Pitié Salpêtrière; Department of Pediatric Neurosurgery (M.C., S.F.-S., C.B., E.R., S.R., G.D., R.C.), Rothschild Foundation Hospital EPICARE; Department of Medical Genetics (J.-M.D.S.A., E.L.), AP-HP, Sorbonne Université, Hôpital de la Pitié Salpêtrière; and Université de Paris Cité (H.A.-B.), service d'Anatomie Pathologique, AP-HP, Hôpital Lariboisière, DMU DREAM, Biobank BB-0033-00064, UMR 1141, INSERM, Paris, France.
ORCID: 0009-0004-3651-8706

Sarah Rosenberg (S)

From the Institut du Cerveau-Paris Brain Institute-ICM (L.S., M.D., J.-M.D.S.A., E.L., Sara Baldassari, Stephanie Baulac), Sorbonne Université, Inserm, CNRS, Hôpital de la Pitié Salpêtrière; Department of Pediatric Neurosurgery (M.C., S.F.-S., C.B., E.R., S.R., G.D., R.C.), Rothschild Foundation Hospital EPICARE; Department of Medical Genetics (J.-M.D.S.A., E.L.), AP-HP, Sorbonne Université, Hôpital de la Pitié Salpêtrière; and Université de Paris Cité (H.A.-B.), service d'Anatomie Pathologique, AP-HP, Hôpital Lariboisière, DMU DREAM, Biobank BB-0033-00064, UMR 1141, INSERM, Paris, France.
ORCID: 0009-0008-5783-0159

Georg Dorfmuller (G)

From the Institut du Cerveau-Paris Brain Institute-ICM (L.S., M.D., J.-M.D.S.A., E.L., Sara Baldassari, Stephanie Baulac), Sorbonne Université, Inserm, CNRS, Hôpital de la Pitié Salpêtrière; Department of Pediatric Neurosurgery (M.C., S.F.-S., C.B., E.R., S.R., G.D., R.C.), Rothschild Foundation Hospital EPICARE; Department of Medical Genetics (J.-M.D.S.A., E.L.), AP-HP, Sorbonne Université, Hôpital de la Pitié Salpêtrière; and Université de Paris Cité (H.A.-B.), service d'Anatomie Pathologique, AP-HP, Hôpital Lariboisière, DMU DREAM, Biobank BB-0033-00064, UMR 1141, INSERM, Paris, France.
ORCID: 0000-0002-4503-6184

Rayann Checri (R)

From the Institut du Cerveau-Paris Brain Institute-ICM (L.S., M.D., J.-M.D.S.A., E.L., Sara Baldassari, Stephanie Baulac), Sorbonne Université, Inserm, CNRS, Hôpital de la Pitié Salpêtrière; Department of Pediatric Neurosurgery (M.C., S.F.-S., C.B., E.R., S.R., G.D., R.C.), Rothschild Foundation Hospital EPICARE; Department of Medical Genetics (J.-M.D.S.A., E.L.), AP-HP, Sorbonne Université, Hôpital de la Pitié Salpêtrière; and Université de Paris Cité (H.A.-B.), service d'Anatomie Pathologique, AP-HP, Hôpital Lariboisière, DMU DREAM, Biobank BB-0033-00064, UMR 1141, INSERM, Paris, France.
ORCID: 0009-0006-9113-6254

Jean-Madeleine De Sainte Agathe (JM)

From the Institut du Cerveau-Paris Brain Institute-ICM (L.S., M.D., J.-M.D.S.A., E.L., Sara Baldassari, Stephanie Baulac), Sorbonne Université, Inserm, CNRS, Hôpital de la Pitié Salpêtrière; Department of Pediatric Neurosurgery (M.C., S.F.-S., C.B., E.R., S.R., G.D., R.C.), Rothschild Foundation Hospital EPICARE; Department of Medical Genetics (J.-M.D.S.A., E.L.), AP-HP, Sorbonne Université, Hôpital de la Pitié Salpêtrière; and Université de Paris Cité (H.A.-B.), service d'Anatomie Pathologique, AP-HP, Hôpital Lariboisière, DMU DREAM, Biobank BB-0033-00064, UMR 1141, INSERM, Paris, France.
ORCID: 0000-0002-7753-8226

Eric Leguern (E)

From the Institut du Cerveau-Paris Brain Institute-ICM (L.S., M.D., J.-M.D.S.A., E.L., Sara Baldassari, Stephanie Baulac), Sorbonne Université, Inserm, CNRS, Hôpital de la Pitié Salpêtrière; Department of Pediatric Neurosurgery (M.C., S.F.-S., C.B., E.R., S.R., G.D., R.C.), Rothschild Foundation Hospital EPICARE; Department of Medical Genetics (J.-M.D.S.A., E.L.), AP-HP, Sorbonne Université, Hôpital de la Pitié Salpêtrière; and Université de Paris Cité (H.A.-B.), service d'Anatomie Pathologique, AP-HP, Hôpital Lariboisière, DMU DREAM, Biobank BB-0033-00064, UMR 1141, INSERM, Paris, France.
ORCID: 0000-0003-0013-9646

Homa Adle-Biassette (H)

From the Institut du Cerveau-Paris Brain Institute-ICM (L.S., M.D., J.-M.D.S.A., E.L., Sara Baldassari, Stephanie Baulac), Sorbonne Université, Inserm, CNRS, Hôpital de la Pitié Salpêtrière; Department of Pediatric Neurosurgery (M.C., S.F.-S., C.B., E.R., S.R., G.D., R.C.), Rothschild Foundation Hospital EPICARE; Department of Medical Genetics (J.-M.D.S.A., E.L.), AP-HP, Sorbonne Université, Hôpital de la Pitié Salpêtrière; and Université de Paris Cité (H.A.-B.), service d'Anatomie Pathologique, AP-HP, Hôpital Lariboisière, DMU DREAM, Biobank BB-0033-00064, UMR 1141, INSERM, Paris, France.
ORCID: 0000-0001-9446-8306

Sara Baldassari (S)

From the Institut du Cerveau-Paris Brain Institute-ICM (L.S., M.D., J.-M.D.S.A., E.L., Sara Baldassari, Stephanie Baulac), Sorbonne Université, Inserm, CNRS, Hôpital de la Pitié Salpêtrière; Department of Pediatric Neurosurgery (M.C., S.F.-S., C.B., E.R., S.R., G.D., R.C.), Rothschild Foundation Hospital EPICARE; Department of Medical Genetics (J.-M.D.S.A., E.L.), AP-HP, Sorbonne Université, Hôpital de la Pitié Salpêtrière; and Université de Paris Cité (H.A.-B.), service d'Anatomie Pathologique, AP-HP, Hôpital Lariboisière, DMU DREAM, Biobank BB-0033-00064, UMR 1141, INSERM, Paris, France.
ORCID: 0000-0003-4851-2796

Stephanie Baulac (S)

From the Institut du Cerveau-Paris Brain Institute-ICM (L.S., M.D., J.-M.D.S.A., E.L., Sara Baldassari, Stephanie Baulac), Sorbonne Université, Inserm, CNRS, Hôpital de la Pitié Salpêtrière; Department of Pediatric Neurosurgery (M.C., S.F.-S., C.B., E.R., S.R., G.D., R.C.), Rothschild Foundation Hospital EPICARE; Department of Medical Genetics (J.-M.D.S.A., E.L.), AP-HP, Sorbonne Université, Hôpital de la Pitié Salpêtrière; and Université de Paris Cité (H.A.-B.), service d'Anatomie Pathologique, AP-HP, Hôpital Lariboisière, DMU DREAM, Biobank BB-0033-00064, UMR 1141, INSERM, Paris, France.
ORCID: 0000-0001-6430-4693

Classifications MeSH