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Open AccessArticle

Simultaneous Detection of NF1, SPRED1, LZTR1, and NF2 Gene Mutations by Targeted NGS in an Italian Cohort of Suspected NF1 Patients

1
Molecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20133 Milan, Italy
2
Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20133 Milan, Italy
3
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza dell’Ateneo Nuovo, 1, 20126 Milan, Italy
4
Molecular Immunology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 20133 Milan, Italy
5
Medical Genetics Unit, Woman-Child-Newborn Department, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, via Francesco Sforza 28, 20122 Milan, Italy
6
Pediatric Highly Intensive Care Unit, Università degli Studi di Milano, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, via Francesco Sforza 28, 20122 Milan, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Genes 2020, 11(6), 671; https://doi.org/10.3390/genes11060671
Received: 23 May 2020 / Revised: 12 June 2020 / Accepted: 16 June 2020 / Published: 19 June 2020
(This article belongs to the Section Human Genomics and Genetic Diseases)
Neurofibromatosis type 1 (NF1) displays overlapping phenotypes with other neurocutaneous diseases such as Legius Syndrome. Here, we present results obtained using a next generation sequencing (NGS) panel including NF1, NF2, SPRED1, SMARCB1, and LZTR1 genes on Ion Torrent. Together with NGS, the Multiplex Ligation-Dependent Probe Amplification Analysis (MLPA) method was performed to rule out large deletions/duplications in NF1 gene; we validated the MLPA/NGS approach using Sanger sequencing on DNA or RNA of both positive and negative samples. In our cohort, a pathogenic variant was found in 175 patients; the pathogenic variant was observed in NF1 gene in 168 cases. A SPRED1 pathogenic variant was also found in one child and in a one year old boy, both NF2 and LZTR1 pathogenic variants were observed; in addition, we identified five LZTR1 pathogenic variants in three children and two adults. Six NF1 pathogenic variants, that the NGS analysis failed to identify, were detected on RNA by Sanger. NGS allows the identification of novel mutations in five genes in the same sequencing run, permitting unambiguous recognition of disorders with overlapping phenotypes with NF1 and facilitating genetic counseling and a personalized follow-up. View Full-Text
Keywords: neurofibromatosis type 1; targeted next generation sequencing (NGS); NF1, SPRED1, LZTR1, NF2 genes pathogenic variants; schwannomatosis neurofibromatosis type 1; targeted next generation sequencing (NGS); NF1, SPRED1, LZTR1, NF2 genes pathogenic variants; schwannomatosis
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Bianchessi, D.; Ibba, M.C.; Saletti, V.; Blasa, S.; Langella, T.; Paterra, R.; Cagnoli, G.A.; Melloni, G.; Scuvera, G.; Natacci, F.; Cesaretti, C.; Finocchiaro, G.; Eoli, M. Simultaneous Detection of NF1, SPRED1, LZTR1, and NF2 Gene Mutations by Targeted NGS in an Italian Cohort of Suspected NF1 Patients. Genes 2020, 11, 671.

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