Recurrent NF1 gene variants and their genotype/phenotype correlations in patients with Neurofibromatosis type I.
NF1 gene pathogenic variants
Neurofibromatosis type I
genotype/phenotype
Journal
Genes, chromosomes & cancer
ISSN: 1098-2264
Titre abrégé: Genes Chromosomes Cancer
Pays: United States
ID NLM: 9007329
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
20
08
2021
received:
27
04
2021
accepted:
23
08
2021
pubmed:
25
8
2021
medline:
19
3
2022
entrez:
24
8
2021
Statut:
ppublish
Résumé
Neurofibromatosis type I, a genetic condition due to pathogenic variants in the NF1 gene, is burdened by a high rate of complications, including neoplasms, which increase morbidity and mortality for the disease. We retrospectively re-evaluated the NF1 gene variants found in the period 2000-2019 and we studied for genotype/phenotype correlations of disease complications and neoplasms 34 variants, which were shared by at least two unrelated families (range 2-11) for a total 141 of probands and 21 relatives affected by Neurofibromatosis type I. Recurrent variants could be ascribed to the most common mutational mechanisms (C to T transition, microsatellite slippage, non-homologous recombination). In genotype/phenotype correlations, the variants p.Arg440*, p.Tyr489Cys, and p.Arg1947*, together with the gross gene deletions, displayed the highest rates of complications. When considering neoplasms, carriers of variants falling in the extradomain region at the 5' end of NF1 had a lower age-related cancer frequency than the rest of the gene sequence, showing a borderline significance (p = 0.045), which was not conserved after correction with covariates. We conclude that (1) hotspots in NF1 occur via different mutational mechanisms, (2) several variants are associated with high rates of complications and cancers, and (3) there is an initial evidence toward a lower cancer risk for carriers of variants in the 5' end of the NF1 gene although not significant at the multivariate analysis.
Identifiants
pubmed: 34427956
doi: 10.1002/gcc.22997
pmc: PMC9291954
doi:
Substances chimiques
NF1 protein, human
0
Neurofibromin 1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10-21Informations de copyright
© 2021 The Authors. Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.
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