NF2 -related schwannomatosis and other schwannomatosis: an updated genetic and epidemiological study.

Autor:	Forde C; Clinical Genetics Service, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK., Smith MJ; Genetic Medicine, University of Manchester, Manchester, UK., Burghel GJ; Genomic Diagnostic Laboratory, Manchester University NHS Foundation Trust, Manchester, UK., Bowers N; North West Genomic Laboratory Hub, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK., Roberts N; Genomic Medicine, MFT, Manchester, UK., Lavin T; Department of Neurology, Manchester Academic Health Sciences Centre (MAHSC), Manchester, UK., Halliday J; Department of Neurosurgery, Salford Royal Hospital, Salford, UK., King AT; Department of Neurosurgery, Salford Royal Hospital, Salford, UK., Rutherford S; Department of Neurosurgery, Salford Royal Hospital, Salford, UK., Pathmanaban ON; Department of Neurosurgery, Salford Royal Hospital, Salford, UK., Lloyd S; Department of Otolaryngology, University of Manchester, Manchester, UK., Freeman S; Otolaryngology, Salford Royal NHS Foundation Trust, Salford, UK., Halliday D; Oxford Centre for Genetic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.; Neurosciences, NF2 Unit, Oxford, UK., Parry A; Department of Neurology, Oxford Radcliffe Hospitals NHS Trust, Oxford, UK., Axon P; Department of Otolaryngology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Buttimore J; Department of Otolaryngology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Afridi S; Guy's and St Thomas' Hospitals NHS Trust, London, UK., Obholzer R; ENT and Skull Base Surgery, Guy's and St Thomas' NHS Foundation Trust, London, UK., Laitt R; Northern Care Alliance NHS Foundation Trust, Salford, Manchester, UK., Thomas O; Department of Neuroradiology, Salford Royal Hospital, Salford, UK., Stivaros SM; Centre for Imaging Sciences, Institute of Population Health, University of Manchester, Manchester, UK.; Academic Unit of Paediatric Radiology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Academic Health Sciences Centre, Manchester, UK., Vassallo G; Department of Paediatric Neurology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK., Evans DG; Neurosurgery, Northern Care Alliance NHS Foundation Trust, Salford, Manchester, UK gareth.d.evans@manchester.ac.uk.; The University of Manchester, Manchester, UK.
Jazyk:	angličtina
Zdroj:	Journal of medical genetics [J Med Genet] 2024 Aug 29; Vol. 61 (9), pp. 856-860. Date of Electronic Publication: 2024 Aug 29.
DOI:	10.1136/jmg-2024-110065
Abstrakt:	Objectives: New diagnostic criteria for NF2-related schwannomatosis (NF2) were published in 2022. An updated UK prevalence was generated in accordance with these, with an emphasis on the rate of de novo NF2 (a 50% frequency is widely quoted in genetic counselling). The distribution of variant types among de novo and familial NF2 cases was also assessed. Methods: The UK National NF2 database identifies patients meeting updated NF2 criteria from a highly ascertained population cared for by England's specialised service. Diagnostic prevalence was assessed on 1 February 2023. Molecular analysis of blood and, where possible, tumour specimens for NF2, LZTR1 and SMARCB1 was performed. Results: 1084 living NF2 patients were identified on prevalence day (equivalent to 1 in 61 332). The proportion with NF2 inherited from an affected parent was only 23% in England. If people without a confirmed molecular diagnosis or bilateral vestibular schwannoma are excluded, the frequency of de novo NF2 remains high (72%). Of the identified de novo cases, almost half were mosaic. The most common variant type was nonsense variants, accounting for 173/697 (24.8%) of people with an established variant, but only 18/235 (7.7%) with an inherited NF2 pathogenic variant (p<0.0001). Missense variants had the highest proportion of familial association (56%). The prevalence of LZTR1 -related schwannomatosis and SMARCB1 -related schwannomatosis was 1 in 527 000 and 1 in 1.1M, respectively, 8.4-18.4 times lower than NF2. Conclusions: This work confirms a much higher rate of de novo NF2 than previously reported and highlights the benefits of maintaining patient databases for accurate counselling. Competing Interests: Competing interests: DGE has received consultancy fees from AstraZeneca, Springworks and Everything Genetic Ltd. (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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