Identification of a recurrent mosaic KRAS variant in brain tissue from an individual with nevus sebaceous syndrome.

Autor:	Green TE; Epilepsy Research Centre, Department of Medicine (Austin Hospital), University of Melbourne, Heidelberg, Victoria, Australia 3084., MacGregor D; Anatomical Pathology, The Royal Children's Hospital, Parkville, Victoria, Australia 3052., Carden SM; Department of Ophthalmology, The Royal Children's Hospital, Parkville, Victoria, Australia 3052.; Department of Ophthalmology, The Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia 3002.; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia 3052., Harris RV; Epilepsy Research Centre, Department of Medicine (Austin Hospital), University of Melbourne, Heidelberg, Victoria, Australia 3084., Hewitt CA; Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia 3000., Berkovic SF; Epilepsy Research Centre, Department of Medicine (Austin Hospital), University of Melbourne, Heidelberg, Victoria, Australia 3084., Penington AJ; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia 3052.; Murdoch Children's Research Institute, Parkville, Victoria, Australia 3052.; Plastic and Maxillofacial Surgery Department, The Royal Children's Hospital, Melbourne, Australia 3052., Scheffer IE; Epilepsy Research Centre, Department of Medicine (Austin Hospital), University of Melbourne, Heidelberg, Victoria, Australia 3084.; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia 3052.; Murdoch Children's Research Institute, Parkville, Victoria, Australia 3052.; Departments of Paediatrics and Neurology, Austin Health, Heidelberg, Victoria, Australia 3084., Hildebrand MS; Epilepsy Research Centre, Department of Medicine (Austin Hospital), University of Melbourne, Heidelberg, Victoria, Australia 3084.; Murdoch Children's Research Institute, Parkville, Victoria, Australia 3052.
Jazyk:	angličtina
Zdroj:	Cold Spring Harbor molecular case studies [Cold Spring Harb Mol Case Stud] 2021 Dec 09; Vol. 7 (6). Date of Electronic Publication: 2021 Dec 09 (Print Publication: 2021).
DOI:	10.1101/mcs.a006133
Abstrakt:	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. (© 2021 Green et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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