Song Su, Yuexia Bai, Yi Lu, Ying Ren, Wenchao Zhang, Guangyu Wang, Kai Ma, Hongwei Zhang
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Selumetinib Treatment in a Neurofibromatosis Type 1 Child With Second Hit Mutation on the NF1 Gene
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder, with plexiform neurofibromas occurring in approximately 20%–50% of patients. A 12-year-old girl underwent surgery due to unbearable pain caused by diffuse neurofibromas. Postoperatively, the girl exhibited rapid growth and extremely extensive plexiform neurofibromas, with multiple plexiform neurofibromas that were inoperable. Through high-throughput sequencing (HTS), genetic molecular analysis was conducted on the peripheral blood samples of the child, and it was found that there was a splice site mutation c.3113 + 1G > A in the NF1 gene. Additionally, we identified a pathogenic variant c.2033dup (Ile679Aspfs*21), citing ClinVar and PMID: 77655472 to confirm its established pathogenicity in the paraffin-embedded section sample of the diffuse neurofibroma, which was exclusively found in the girl's plexiform neurofibroma. This ‘second-hit’ mutation could explain the rapid growth of the diffuse neurofibroma. The patient was effectively treated with oral administration of the selective MEK inhibitor selumetinib, resulting in rapid tumour regression. The treatment has shown promising efficacy against the rapid tumour growth induced by the patient's ‘second-hit’ mutation.
期刊介绍:
International Journal of Developmental Neuroscience publishes original research articles and critical review papers on all fundamental and clinical aspects of nervous system development, renewal and regeneration, as well as on the effects of genetic and environmental perturbations of brain development and homeostasis leading to neurodevelopmental disorders and neurological conditions. Studies describing the involvement of stem cells in nervous system maintenance and disease (including brain tumours), stem cell-based approaches for the investigation of neurodegenerative diseases, roles of neuroinflammation in development and disease, and neuroevolution are also encouraged. Investigations using molecular, cellular, physiological, genetic and epigenetic approaches in model systems ranging from simple invertebrates to human iPSC-based 2D and 3D models are encouraged, as are studies using experimental models that provide behavioural or evolutionary insights. The journal also publishes Special Issues dealing with topics at the cutting edge of research edited by Guest Editors appointed by the Editor in Chief. A major aim of the journal is to facilitate the transfer of fundamental studies of nervous system development, maintenance, and disease to clinical applications. The journal thus intends to disseminate valuable information for both biologists and physicians. International Journal of Developmental Neuroscience is owned and supported by The International Society for Developmental Neuroscience (ISDN), an organization of scientists interested in advancing developmental neuroscience research in the broadest sense.