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

• DOI: 10.1038/s41431-021-01015-4
• Publication Date: 2021-12-13T02:02:42Z
• Authors: Claire Forde; Emma Burkitt-Wright; Peter D. Turnpenny; Eric Haan; John Ealing; Sahar Mansour; Muriel Holder; Nayana Lahiri; Abhijit Dixit; Annie Procter; Laurence Pacot; Dominique Vidaud; Yline Capri; Marion Gerard; Hélène Dollfus; Elise Schaefer; Chloé Quelin; Sabine Sigaudy; Tiffany Busa; Gabriella Vera; Lena Damaj; Ludwine Messiaen; David A. Stevenson; Peter Davies; Sheila Palmer-Smith; Alison Callaway; Pierre Wolkenstein; Eric Pasmant; Meena Upadhyaya
• Keywords: 0303 health sciences; 03 medical and health sciences; Neurofibroma; Neurofibromatosis 1; Cafe-au-Lait Spots; Humans; [SDV.GEN] Life Sciences [q-bio]/Genetics; Longitudinal Studies; Article; Genetic Association Studies; 3. Good health

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