ArticleAnnals of clinical and translational neurology2016
Somatic mutations in GLI3 and OFD1 involved in sonic hedgehog signaling cause hypothalamic hamartoma.
Article in Annals of clinical and translational neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- A novel ZNF263-SMOX-ROS-TRIB3 signaling axis drives Wnt/β-catenin activation and metastatic progression in colorectal cancer.Apoptosis : an international journal on programmed cell death · 2026Article
- Merritt-Putnam Symposium | Tumor-Associated Epilepsy and Epilepsy-Associated Tumors: Exploring the Bidirectional Crosstalk Between Tumors and Seizures.Epilepsy currents · 2026Article
- Developmental and epileptic encephalopathy in patients with epilepsy due to hypothalamic hamartomas.Epilepsia · 2025Article
- Somatic variants as a cause of drug-resistant epilepsy including mesial temporal lobe epilepsy with hippocampal sclerosis.Epilepsia · 2024Article
- Advances in epileptic network findings of hypothalamic hamartomas.Journal of central nervous system disease · 2024Review
- Clinical and molecular heterogeneity of syndromic hypothalamic hamartoma.American journal of medical genetics. Part A · 2023Article
- Genetic Disruption of Cilia-Associated Signaling Pathways in Patients with VACTERL Association.Children (Basel, Switzerland) · 2023Article
- Incomplete hippocampal inversion in patients with mutations in genes involved in sonic hedgehog signaling.Heliyon · 2023Article
- Pulmonary hamartoma in an elk calf.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2023Article
- Cytogenomic epileptology.Molecular cytogenetics · 2023Review
- The hidden hedgehog of the pituitary: hedgehog signaling in development, adulthood and disease of the hypothalamic-pituitary axis.Frontiers in endocrinology · 2023Review
- Mosaic variants detectable in blood extend the clinicogenetic spectrum ofGenetics in medicine open · 2023Article
- Somatic mosaicism in the diseased brain.Molecular cytogenetics · 2022Review
- Sporadic hypothalamic hamartoma is a ciliopathy with somatic and bi-allelic contributions.Human molecular genetics · 2022Article
- Contribution of Smoothened Receptor Signaling in GABAergic Neurotransmission and Chloride Homeostasis in the Developing Rodent Brain.Frontiers in physiology · 2021Review
- A zinc finger family protein, ZNF263, promotes hepatocellular carcinoma resistance to apoptosis via activation of ER stress-dependent autophagy.Translational oncology · 2020Article
- Somatic variants in epilepsy - advancing gene discovery and disease mechanisms.Current opinion in genetics & development · 2020Review
- Cellular and developmental basis of orofacial clefts.Birth defects research · 2020Review
- Smoothened receptor signaling regulates the developmental shift of GABA polarity in rat somatosensory cortex.Journal of cell science · 2020Article
- Hypothalamic hamartomas and inner ear diverticula with X-linked stapes gusher syndrome - new associations?Pediatric radiology · 2020Article
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Authors and funding
14 authors.
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Abstract
objectiveHypothalamic hamartoma (HH) is a congenital anomalous brain tumor. Although most HHs are found without any other systemic features, HH is observed in syndromic disorders such as Pallister-Hall syndrome (PHS) and oral-facial-digital syndrome (OFD). Here, we explore the possible involvement of somatic mutations in HH.
methodsWe analyzed paired blood and hamartoma samples from 18 individuals, including three with digital anomalies, by whole-exome sequencing. Detected somatic mutations were validated by Sanger sequencing and deep sequencing of target amplicons. The effect of GLI3 mutations on its transcriptional properties was evaluated by luciferase assays using reporters containing eight copies of the GLI-binding site and a mutated control sequence disrupting GLI binding.
resultsWe found hamartoma-specific somatic truncation mutations in GLI3 and OFD1, known regulators of sonic hedgehog (Shh) signaling, in two and three individuals, respectively. Deep sequencing of amplicons covering the mutations showed mutant allele rates of 7-54%. Somatic mutations in OFD1 at Xp22 were found only in male individuals. Potential pathogenic somatic mutations in UBR5 and ZNF263 were also identified in each individual. Germline nonsense mutations in GLI3 and OFD1 were identified in each individual with PHS and OFD type I in our series, respectively. The truncated GLI3 showed stronger repressor activity than the wild-type protein. We did not detect somatic mutations in the remaining 9 individuals.
interpretationOur data indicate that a spectrum of human disorders can be caused by lesion-specific somatic mutations, and suggest that impaired Shh signaling is one of the pathomechanisms of HH.
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