Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/33572
Title: Brain mosaicism of hedgehog signalling and other cilia genes in hypothalamic hamartoma.
Austin Authors: Green, Timothy E;Fujita, Atsushi;Ghaderi, Navid;Heinzen, Erin L;Matsumoto, Naomichi;Klein, Karl Martin;Berkovic, Samuel F ;Hildebrand, Michael S 
Affiliation: Epilepsy Research Centre
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Departments of Clinical Neurosciences, Medical Genetics and Community Health Sciences, Hotchkiss Brain Institute & Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Canada.
Eshelman School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics, Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Departments of Clinical Neurosciences, Medical Genetics and Community Health Sciences, Hotchkiss Brain Institute & Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Canada; Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe University and University Hospital Frankfurt, Frankfurt am Main, Germany; LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe University Frankfurt, Frankfurt am Main, Germany.
Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
Issue Date: 12-Aug-2023
Date: 2023
Publication information: Neurobiology of Disease 2023-08-12; 185
Abstract: Hypothalamic hamartoma (HH) is a rare benign developmental brain lesion commonly associated with a well characterized epilepsy phenotype. Most individuals with HH are non-syndromic without additional developmental anomalies nor a family history of disease. Nonetheless, HH is a feature of Pallister-Hall (PHS) and Oro-Facial-Digital Type VI (OFD VI) syndromes, both characterized by additional developmental anomalies. Initial genetic of analysis HH began with syndromic HH, where germline inherited or de novo variants in GLI3, encoding a central transcription factor in the sonic hedgehog (Shh) signalling pathway, were identified in most individuals with PHS. Following these discoveries in syndromic HH, the hypothesis that post-zygotic mosaicism in related genes may underly non-syndromic HH was tested. We discuss the identified mosaic variants within individuals with non-syndromic HH, review the analytical methodologies and diagnostic yields, and explore understanding of the functional role of the implicated genes with respect to Shh signalling, and cilia development and function. We also outline future challenges in studying non-syndromic HH and suggest potential novel strategies to interrogate brain mosaicism in HH.
URI: https://ahro.austin.org.au/austinjspui/handle/1/33572
DOI: 10.1016/j.nbd.2023.106261
ORCID: 
Journal: Neurobiology of Disease
Start page: 106261
PubMed URL: 37579995
ISSN: 1095-953X
Type: Journal Article
Subjects: Hypothalamic hamartoma
Mosaicism
Sonic hedgehog signalling
Appears in Collections:Journal articles

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