ArticleAmerican journal of human genetics2016
Mutations of the Sonic Hedgehog Pathway Underlie Hypothalamic Hamartoma with Gelastic Epilepsy.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 72 citations in OpenAlex.
- Merritt-Putnam Symposium | Tumor-Associated Epilepsy and Epilepsy-Associated Tumors: Exploring the Bidirectional Crosstalk Between Tumors and Seizures.Epilepsy currents · 2026Article
- A novel EVC2 splice-site variant expands the mutational and phenotypic spectrum of Weyers acrofacial dysostosis.BMC medical genomics · 2026Article
- An update in the MRI features, classification, and associated brain abnormalities in hypothalamic hamartomas.BJR open · 2026Article
- Case Report: Phenotypic and genetic characterization of a presumptive sporadic hypothalamic hamartoma in a standard Schnauzer dog.Frontiers in veterinary science · 2025Article
- Human embryonic genetic mosaicism and its effects on development and disease.Nature reviews. Genetics · 2024Review
- Protein Kinase A in neurological disorders.Journal of neurodevelopmental disorders · 2024Review
- Advances in epileptic network findings of hypothalamic hamartomas.Journal of central nervous system disease · 2024Review
- Cytogenomic epileptology.Molecular cytogenetics · 2023Review
- Mosaic variants detectable in blood extend the clinicogenetic spectrum ofGenetics in medicine open · 2023Article
- The hidden hedgehog of the pituitary: hedgehog signaling in development, adulthood and disease of the hypothalamic-pituitary axis.Frontiers in endocrinology · 2023Review
- Somatic mosaicism in the diseased brain.Molecular cytogenetics · 2022Review
- Hypothalamic hamartoma associated with polymicrogyria and periventricular nodular heterotopia in children: report of three cases and discussion of the origin of the seizures.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2022Article
- The changing landscape in epilepsy imaging: Unmasking subtle and unique entities.Diagnostic and interventional radiology (Ankara, Turkey) · 2022Article
- Sporadic hypothalamic hamartoma is a ciliopathy with somatic and bi-allelic contributions.Human molecular genetics · 2022Article
- De Novo GLI3 Pathogenic Variants May Cause Hypotonia and a Range of Brain Malformations Without Skeletal Abnormalities.Pediatric neurology · 2022Article
- CfDNA Measurement as a Diagnostic Tool for the Detection of Brain Somatic Mutations in Refractory Epilepsy.International journal of molecular sciences · 2022Review
- Sonic Hedgehog Signaling in Cerebellar Development and Cancer.Frontiers in cell and developmental biology · 2022Review
- Hypothalamic Hamartomas: Evolving Understanding and Management.Neurology · 2021Review
- Description of a giant hypothalamic hamartoma associated with an immature ruptured giant sacrococcygeal teratoma: a case report.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2021Article
- Contribution of Smoothened Receptor Signaling in GABAergic Neurotransmission and Chloride Homeostasis in the Developing Rodent Brain.Frontiers in physiology · 2021Review
Corrections and comments
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Authors and funding
19 authors at 10 institutions in 3 countries.
Funding
Abstract
Hypothalamic hamartoma (HH) with gelastic epilepsy is a well-recognized drug-resistant epilepsy syndrome of early life.(1) Surgical resection allows limited access to the small deep-seated lesions that cause the disease. Here, we report the results of a search for somatic mutations in paired hamartoma- and leukocyte-derived DNA samples from 38 individuals which we conducted by using whole-exome sequencing (WES), chromosomal microarray (CMA), and targeted resequencing (TRS) of candidate genes. Somatic mutations were identified in genes involving regulation of the sonic hedgehog (Shh) pathway in 14/38 individuals (37%). Three individuals had somatic mutations in PRKACA, which encodes a cAMP-dependent protein kinase that acts as a repressor protein in the Shh pathway, and four subjects had somatic mutations in GLI3, an Shh pathway gene associated with HH. In seven other individuals, we identified two recurrent and three single brain-tissue-specific, large copy-number or loss-of-heterozygosity (LOH) variants involving multiple Shh genes, as well as other genes without an obvious biological link to the Shh pathway. The Shh pathway genes in these large somatic lesions include the ligand itself (SHH and IHH), the receptor SMO, and several other Shh downstream pathway members, including CREBBP and GLI2. Taken together, our data implicate perturbation of the Shh pathway in at least 37% of individuals with the HH epilepsy syndrome, consistent with the concept of a developmental pathway brain disease.
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