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; SF Berkovic; MS Hildebrand

Journal article

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 Show all

Human Molecular Genetics | OXFORD UNIV PRESS | Published : 2022

DOI: 10.1093/hmg/ddab366

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Abstract

Hypothalamic hamartoma with gelastic seizures is a well-established cause of drug-resistant epilepsy in early life. The development of novel surgical techniques has permitted the genomic interrogation of hypothalamic hamartoma tissue. This has revealed causative mosaic variants within GLI3, OFD1 and other key regulators of the sonic-hedgehog pathway in a minority of cases. Sonic-hedgehog signalling proteins localize to the cellular organelle primary cilia. We therefore explored the hypothesis that cilia gene variants may underlie hitherto unsolved cases of sporadic hypothalamic hamartoma. We performed high-depth exome sequencing and chromosomal microarray on surgically resected hypothalamic ..

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University of Melbourne Researchers

Mark Bennett Author

Caitlin Bennett Author

Rick Leventer Author

Simon Harvey Author

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Grants

Awarded by National Institute of Neurological Disorders and Stroke

Funding Acknowledgements

National Health and Medical Research Council Program Grant (1091593) to I.E.S. and S.F.B., a Project Grant (1129054) to S.F.B., a Project Grant (1079058) to M.S.H., a Practitioner Fellowship (1006110) to I.E.S., a Senior Research Fellowship (1102971) to M.B., and a R.D Wright Career Development Fellowship (1063799) to M.S.H. R.J.L. is supported by a Melbourne Children's Clinician Scientist Fellowship and P. J.L. is supported by the Vincent Ciodo Foundation. Z.Y. is supported by a University of Melbourne Australian Postgraduate Award International Graduate Research Training Scholarship, and a private scholarship from the Tang Lixin Education Development Fund. I.E.S. was also funded by grants from the National Institutes of Health, Australian Research Council, Health Research Council of NewZealand, CURE, AmericanEpilepsySociety, US Department of Defense AutismSpectrumDisorderResearchProgram, MarchofDimesandPerpetualCharitableTrustees. E.L.H. wassupportedbyaNationalInstitutesofHealthgrant(R21-NS078657). J.E.M. issupportedbytheNationalInstitutesofHealth(TL1TR001875). ThisworkwasmadepossiblethroughVictorianStateGovernmentOperationalInfrastructureSupportandAustralianGovernmentNHMRCIRIISS. ThisstudywassupportedbyaCureKids(3576) 15/070projectgranttoL. G.S. M.F.BwassupportedbyaTakingFlightAwardfromCUREEpilepsy. AuthorContribution