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Open AccessArticle

Clinical and Genetic Findings in Children with Neurofibromatosis Type 1, Legius Syndrome, and Other Related Neurocutaneous Disorders

1
Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via L. De Crecchio 7, 80138 Napoli, Italy
2
Departement of Women’s and Children’s Health and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Via Luigi De Crecchio 2, 80138 Napoli, Italy
3
Department of Medical Sciences and Advanced Surgery, University of Campania “Luigi Vanvitelli”, Piazza L. Miraglia 2, 80138 Napoli, Italy
4
Department of Pediatrics, University of Naples “Federico II”, Via Pansini 5, 80131 Napoli, Italy
5
Dermatology Unit, University of Campania “Luigi Vanvitelli”, Via Pansini 5, 80131 Napoli, Italy
6
Department of Translational Medicine, University of Campania “Luigi Vanvitelli”, Via L. Bianchi c/o Ospedale Monaldi, 80131 Napoli, Italy
7
Department of Neurosciences, "Santobono-Pausilipon" Pediatric Hospital, Via Fiore 6, 80129 Napoli, Italy
8
Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli, Italy
*
Author to whom correspondence should be addressed.
Both authors contributed equally to this work.
Genes 2019, 10(8), 580; https://doi.org/10.3390/genes10080580
Received: 26 June 2019 / Revised: 27 July 2019 / Accepted: 30 July 2019 / Published: 31 July 2019
(This article belongs to the Special Issue Neurofibromatosis 1 Genetics)
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Abstract

Pigmentary manifestations can represent an early clinical sign in children affected by Neurofibromatosis type 1 (NF1), Legius syndrome, and other neurocutaneous disorders. The differential molecular diagnosis of these pathologies is a challenge that can now be met by combining next generation sequencing of target genes with concurrent second-level tests, such as multiplex ligation-dependent probe amplification and RNA analysis. We clinically and genetically investigated 281 patients, almost all pediatric cases, presenting with either NF1 (n = 150), only pigmentary features (café au lait macules with or without freckling; (n = 95), or clinical suspicion of other RASopathies or neurocutaneous disorders (n = 36). The causative variant was identified in 239 out of the 281 patients analyzed (85.1%), while 42 patients remained undiagnosed (14.9%). The NF1 and SPRED1 genes were mutated in 73.3% and 2.8% of cases, respectively. The remaining 8.9% carried mutations in different genes associated with other disorders. We achieved a molecular diagnosis in 69.5% of cases with only pigmentary manifestations, allowing a more appropriate clinical management of these patients. Our findings, together with the increasing availability and sharing of clinical and genetic data, will help to identify further novel genotype–phenotype associations that may have a positive impact on patient follow-up. View Full-Text
Keywords: neurofibromatosis type 1; Legius syndrome; RASopathies; next generation sequencing; multiplex ligation-dependent probe amplification; RNA analysis neurofibromatosis type 1; Legius syndrome; RASopathies; next generation sequencing; multiplex ligation-dependent probe amplification; RNA analysis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Giugliano, T.; Santoro, C.; Torella, A.; Del Vecchio Blanco, F.; Grandone, A.; Onore, M.E.; Melone, M.A.B.; Straccia, G.; Melis, D.; Piccolo, V.; Limongelli, G.; Buono, S.; Perrotta, S.; Nigro, V.; Piluso, G. Clinical and Genetic Findings in Children with Neurofibromatosis Type 1, Legius Syndrome, and Other Related Neurocutaneous Disorders. Genes 2019, 10, 580.

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