Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/28613
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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