Prevalence of NF1 missense mutations and candidate modifier genes in 12 familial and 15 sporadic spinal neurofibromatosis patients
Abstract
Data di Pubblicazione:
2020
Citazione:
Prevalence of NF1 missense mutations and candidate modifier genes in 12 familial and 15 sporadic spinal neurofibromatosis patients / P. Riva, E. Mangano, C. Cesaretti, P. Bettinaglio, R. Bordoni, V. Tritto, C. Battaglia, V. Saletti, D. Bianchessi, M. Marina Melone, C. Schettino, F. Natacci, M. Eoli. - In: EUROPEAN JOURNAL OF HUMAN GENETICS. - ISSN 1476-5438. - 28:Supplement 1(2020 Dec 01), pp. P11.90.C.482-P11.90.C.482. (Intervento presentato al 53. convegno ESHG European Society of Human Genetics (ESHG) Conference: Interactive e-Posters December tenutosi a Virtual Conference nel 2020).
Abstract:
Spinal Neurofibromatosis (SNF) is a specific form of Neurofibromatosis type 1 (NF1) characterized by bilateral neurofibromas involving all spinal roots. This feature allows to specifically distinguish SNF from Neurofibromatosis type 1 (NF1), and Multiple Neurofibromas Few Spinal Root (MNFSR), presenting single/few isolated spinal neurofi- bromas. While the clinical phenotype of SNF, MNSFR and classical NF1 can be revealed by spinal MRI, little is known on the molecular basis underlying these conditions. We investigated 12 NF1 families with at least one SNF patient, 15 sporadic SNF/MNSFR patients, diagnosed by Spinal MRI. We applied Targeted NGS using a panel consisting of 139 genes encoding RAS pathway effectors, neurofibromin interactors and genes mapping at 17q11.2 region. On identified 26 NF1 variants, 36,6% were missense mutations, indicating an increased prevalence in our cohort versus 27,7% missense/nonsense mutations reported in Italian (PMID: 26740943) and in a British (PMID:28637487) NF1 population. Furthermore, we evaluated rare variants with damaging predictors in genes of RAS pathway and neuro- fibromin interactors. In more than one sporadic case pos- sible pathogenic variants were found in LIMK2, RASAL1, RASAL3, SOS1, A2ML1, MAP3K1, while in more than one SNF family were detected RASAL1, RASAL3, MAP3K1 genes variations. Our results confirm the high frequency of missense mutations in SNF as reported (PMID: 26740943, PMID:25211147), indicating neurofi- bromin gain-of-function variants as associated to SNF. In some patients, the co-occurrence of potential pathogenic variants in NF1 related genes are detected with severe phenotypes, suggesting that they might be modifier genes and promising pharmacological targets. Italian Ministry of Health RF-2016-02361293.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
P. Riva, E. Mangano, C. Cesaretti, P. Bettinaglio, R. Bordoni, V. Tritto, C. Battaglia, V. Saletti, D. Bianchessi, M. Marina Melone, C. Schettino, F. Natacci, M. Eoli
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