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Title: | Identification of a recurrent mosaic KRAS variant in brain tissue from an individual with nevus sebaceous syndrome. | Austin Authors: | Green, Timothy E;MacGregor, Duncan;Carden, Susan M;Harris, Rebekah V;Hewitt, Chelsee A;Berkovic, Samuel F ;Penington, Anthony J;Scheffer, Ingrid E ;Hildebrand, Michael S | Affiliation: | Paediatrics Epilepsy Research Centre Neurology Plastic and Maxillofacial Surgery Department, The Royal Children's Hospital, Melbourne, Australia Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia Department of Ophthalmology, The Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Anatomical Pathology, The Royal Children's Hospital, Parkville, Victoria, Australia Murdoch Children's Research Institute, Parkville, Victoria, Australia Department of Ophthalmology, The Royal Children's Hospital, Parkville, Victoria, Australia |
Issue Date: | 9-Dec-2021 | Date: | 2021-12 | Publication information: | Cold Spring Harbor Molecular Case Studies 2021; 7(6): a006133. | Abstract: | Nevus sebaceous syndrome (NSS) is a rare, multisystem neurocutaneous disorder, characterized by a congenital nevus, and may include brain malformations such as hemimegalencephaly or focal cortical dysplasia, ocular, and skeletal features. It has been associated with several eponyms including Schimmelpenning and Jadassohn. The isolated skin lesion, nevus sebaceous, is associated with postzygotic variants in HRAS or KRAS in all individuals studied. The RAS proteins encode a family of GTPases that form part of the RAS/MAPK signaling pathway, which is critical for cell cycle regulation and differentiation during development. We studied an individual with nevus sebaceous syndrome with an extensive nevus sebaceous, epilepsy, intellectual disability, and hippocampal sclerosis without pathological evidence of a brain malformation. We used high-depth gene panel sequencing and droplet digital polymerase chain reaction (PCR) to detect and quantify RAS/MAPK gene variants in nevus sebaceous and temporal lobe tissue collected during plastic and epilepsy surgery, respectively. A mosaic KRAS c.34G > T; p.(Gly12Cys) variant, also known as G12C, was detected in nevus sebaceous tissue at 25% variant allele fraction (VAF), at the residue most commonly substituted in KRAS Targeted droplet digital PCR validated the variant and quantified the mosaicism in other tissues. The variant was detected at 33% in temporal lobe tissue but was absent from blood and healthy skin. We provide molecular confirmation of the clinical diagnosis of NSS. Our data extends the histopathological spectrum of KRAS G12C mosaicism beyond nevus sebaceous to involve brain tissue and, more specifically, hippocampal sclerosis. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/28613 | DOI: | 10.1101/mcs.a006133 | ORCID: | 0000-0003-4580-841X 0000-0002-2311-2174 0000-0002-6748-9651 0000-0002-2648-7828 0000-0003-2739-0515 |
Journal: | Cold Spring Harbor Molecular Case Studies | PubMed URL: | 34649968 | PubMed URL: | https://pubmed.ncbi.nlm.nih.gov/34649968/ | Type: | Journal Article | Subjects: | focal seizures with impairment of consciousness or awareness generalized tonic seizures intellectual disability linear nevus sebaceous mild |
Appears in Collections: | Journal articles |
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