Natural history of NF1 c.2970_2972del p.(Met992del): confirmation of a low risk of complications in a longitudinal study. - Archive ouverte HAL Access content directly
Journal Articles Eur J Hum Genet Year : 2022

Natural history of NF1 c.2970_2972del p.(Met992del): confirmation of a low risk of complications in a longitudinal study.

Claire Forde
  • Function : Author
Emma Burkitt-Wright
  • Function : Author
Peter D Turnpenny
  • Function : Author
Eric Haan
  • Function : Author
John Ealing
  • Function : Author
Sahar Mansour
  • Function : Author
Muriel Holder
  • Function : Author
Nayana Lahiri
  • Function : Author
Abhijit Dixit
  • Function : Author
Annie Procter
  • Function : Author
Laurence Pacot
  • Function : Author
Dominique Vidaud
  • Function : Author
Yline Capri
  • Function : Author
Marion Gerard
  • Function : Author
Hélène Dollfus
  • Function : Author
  • PersonId : 938002
Elise Schaefer
  • Function : Author
  • PersonId : 1289500
Chloé Quelin
  • Function : Author
Sabine Sigaudy
  • Function : Author
Tiffany Busa
  • Function : Author
Gabriella Vera
  • Function : Author
Lena Damaj
  • Function : Author
Ludwine Messiaen
  • Function : Author
David A Stevenson
  • Function : Author
Peter Davies
  • Function : Author
Sheila Palmer-Smith
  • Function : Author
Alison Callaway
  • Function : Author
Pierre Wolkenstein
  • Function : Author
Eric Pasmant
Meena Upadhyaya
  • Function : Author

Abstract

Individuals with the three base pair deletion NM_000267.3(NF1):c.2970_2972del p.(Met992del) have been recognised to present with a milder neurofibromatosis type 1 (NF1) phenotype characterised by café-au-lait macules (CALs) and intertriginous freckling, as well as a lack of cutaneous, subcutaneous and plexiform neurofibromas and other NF1-associated complications. Examining large cohorts of patients over time with this specific genotype is important to confirm the presentation and associated risks of this variant across the lifespan. Forty-one individuals with the in-frame NF1 deletion p.Met992del were identified from 31 families. Clinicians completed a standardised clinical questionnaire for each patient and the resulting data were collated and compared to published cohorts. Thirteen patients have been previously reported, and updated clinical information has been obtained for these individuals. Both CALs and intertriginous freckling were present in the majority of individuals (26/41, 63%) and the only confirmed features in 11 (27%). 34/41 (83%) of the cohort met NIH diagnostic criteria. There was a notable absence of all NF1-associated tumour types (neurofibroma and glioma). Neurofibroma were observed in only one individual-a subcutaneous lesion (confirmed histologically). Nineteen individuals were described as having a learning disability (46%). This study confirms that individuals with p.Met992del display a mild tumoural phenotype compared to those with 'classical', clinically diagnosed NF1, and this appears to be the case longitudinally through time as well as at presentation. Learning difficulties, however, appear to affect a significant proportion of NF1 subjects with this phenotype. Knowledge of this genotype-phenotype association is fundamental to accurate prognostication for families and caregivers.

Domains

Genetics
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Licence : CC BY - Attribution

Dates and versions

hal-04255330 , version 1 (24-10-2023)

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Claire Forde, Emma Burkitt-Wright, Peter D Turnpenny, Eric Haan, John Ealing, et al.. Natural history of NF1 c.2970_2972del p.(Met992del): confirmation of a low risk of complications in a longitudinal study.. Eur J Hum Genet, 2022, 30 (3), ⟨10.1038/s41431-021-01015-4⟩. ⟨hal-04255330⟩
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