The Role of Co-Deleted Genes in Neurofibromatosis Type 1 Microdeletions: An Evolutive Approach
Abstract
:1. Introduction
2. Methodology
2.1. Background
2.2. Genes and Organisms Selected for Analysis
2.3. Sequence Alignment and Phylogenetic Analyses
2.4. Selection Analysis
3. Results
3.1. Phylogenetic Relationships of the Co-Deleted Genes
3.2. Selection Analysis of the Co-Deleted Genes
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Rasmussen, S.A.; Friedman, J.M. NF1 gene and neurofibromatosis 1. Am. J. Epidemiol. 2000, 151, 33–40. [Google Scholar] [CrossRef] [PubMed]
- National Institutes of Health Consensus Development Conference Statement. Neurofibromatosis. Arch. Neurol. Chic. 1998, 45, 575–578. [Google Scholar]
- The Human Gene Mutation Database. Available online: http://www.hgmd.cf.ac.uk/ac/index.php (accessed on 16 March 2017).
- Messiaen, L.M.; Wimmer, K. NF1 mutational spectrum. Neurofibromatoses. Monogr. Hum. Genet. 2008, 16, 63–77. [Google Scholar]
- Venturin, M.; Guarnieri, P.; Natacci, F.; Stabile, M.; Tenconi, R.; Clementi, M.; Hernandez, C.; Thompson, P.; Upadhyaya, M.; Larizza, L.; et al. Mental retardation and cardiovascular malformations in NF1 microdeleted patients point to candidate genes in 17q11.2. J. Med. Genet. 2004, 41, 35–41. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mensink, K.A.; Ketterling, R.P.; Flynn, H.C.; Knudson, R.A.; Lindor, N.M.; Heese, B.A.; Spinner, R.J.; Babovic-Vuksanovic, D. Connective tissue dysplasia in five new patients with NF1 microdeletions: further expansion of phenotype and review of the literature. J. Med. Genet. 2006, 43, e8. [Google Scholar] [CrossRef] [PubMed]
- De Raedt, T.; Brems, H.; Wolkenstein, P.; Vidaud, D.; Pilotti, S.; Perrone, F.; Mautner, V.; Frahm, S.; Sciot, R.; Legius, E. Elevated risk for MPNST in NF1 microdeletion patients. Am. J. Hum. Genet. 2003, 72, 1288–1292. [Google Scholar] [CrossRef] [PubMed]
- Descheemaeker, M.J.; Roelandts, K.; De Raedt, T.; Brems, H.; Fryns, J.P.; Legius, E. Intelligence in individuals with a neurofibromatosis type 1 microdeletion. Am. J. Med. Genet. 2004, 131, 325–326. [Google Scholar] [CrossRef]
- Zhang, J.; Tong, H.; Fu, X.; Zhang, Y.; Liu, J.; Cheng, R.; Liang, J.; Peng, J.; Sun, Z.; Liu, H.; et al. Molecular characterization of NF1 and neurofibromatosis type 1 genotype- phenotype correlations in a Chinese population. Sci. Rep. 2005, 5, 11291. [Google Scholar] [CrossRef]
- Bartelt-Kirbach, B.; Wuepping, M.; Dodrimont-Lattke, M.; Kaufmann, D. Expression analysis of genes lying in the NF1 microdeletion interval points to four candidate modifiers for neurofibroma formation. Neurogenetics 2009, 10, 79–85. [Google Scholar] [CrossRef]
- Pasmant, E.; Masliah-Planchon, J.; Lévy, P.; Laurendeau, I.; Ortonne, N.; Parfait, B.; Valeyrie-Allanore, L.; Leroy, K.; Wolkenstein, P.; Vidaud, M.; et al. Identification of genes potentially involved in the increased risk of malignancy in NF1-microdeleted patients. Mol. Med. 2011, 17, 79–87. [Google Scholar] [CrossRef]
- Yang, F.; Xu, Y.P.; Li, J.; Duan, S.S.; Fu, Y.J.; Zhang, Y.; Zhao, Y.; Qiao, W.T.; Chen, Q.M.; Geng, Y.Q.; et al. Cloning and characterization of a novel intracellular protein p48.2 that negatively regulates cell cycle progression. Int. J. Biochem. Cell Biol. 2009 41, 2240–2250. [CrossRef]
- Sabbagh, A.; Pasmant, E.; Laurendeau, I.; Parfait, B.; Barbarot, S.; Guillot, B.; Combemale, P.; Ferkal, S.; Vidaud, M.; Aubourg, P. Members of the NF France Network. Unravelling the genetic basis of variable clinical expression in neurofibromatosis 1. Hum. Mol. Genet. 2009, 18, 2768–2778. [Google Scholar] [CrossRef] [PubMed]
- Mautner, V.F.; Kluwe, L.; Friedrich, R.E.; Roehl, A.C.; Bammert, S.; Högel, J.; Spöri, H.; Cooper, D.N.; Kehrer-Sawatzki, H. Clinical characterization of 29 neurofibromatosis type-1 patients with molecularly ascertained 1.4 Mb type-1 NF1 deletions. J. Med. Genet. 2010, 47, 623–630. [Google Scholar] [CrossRef] [PubMed]
- Nielsen, R.C.; Bustamante, A.G.; Clark, S.; Glanowski, T.B.; Sackton, M.J.; Hubisz, A.; Fledel-Alon, A.; Tanenbaum, D.M.; Civello, D.; White, T.J.; et al. A scan for positively selected genes in the genomes of humans and chimpanzees. PLoS Biol. 2005, 3, e170. [Google Scholar] [CrossRef] [PubMed]
- Bustamante, C.D.; Fledel-Alon, A.; Williamson, S.; Nielsen, R.; Hubisz, M.T.; Glanowski, S.; Tanenbaum, D.M.; White, T.J.; Sninsky, J.J.; Hernandez, R.D.; et al. Natural selection on protein-coding genes in the human genome. Nature 2005, 437, 1153–1157. [Google Scholar] [CrossRef]
- Yang, Z. Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution. Mol. Biol. Evol. 1998, 15, 568–573. [Google Scholar] [CrossRef] [PubMed]
- Rosset, C.; Vairo, F.; Bandeira, I.C.; Fonini, M.; Netto, C.B.O.; Ashton-Prolla, P. Clinical and molecular characterization of neurofibromatosis in southern Brazil. Expert. Rev. Mol. Diagn. 2018, 18, 577–586. [Google Scholar] [CrossRef]
- Edgar, R.C. MUSCLE: Multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 2004, 32, 1792–1797. [Google Scholar] [CrossRef]
- Tamura, K.; Stecher, G.; Peterson, D.; Filipski, A.; Kumar, S. MEGA6: Molecular Evolutionary Genetics Analysis Version 6.0. Mol. Biol. Evol. 2013, 30, 2725–2729. [Google Scholar] [CrossRef] [Green Version]
- Drummond, A.J.; Suchard, M.A.; Xie, D.; Rambaut, A. Bayesian phylogenetics with BEAUti and the BEAST 1.7. Mol. Biol. Evol. 2012, 29, 1969–1973. [Google Scholar] [CrossRef]
- Darriba, D.; Taboada, G.L.; Doallo, R.; Posada, D. jModelTest 2: more models, new heuristics and parallel computing. Nat. Methods 2012, 9, 772. [Google Scholar] [CrossRef] [PubMed]
- Abascal, F.; Zardoya, R.; Posada, D. ProtTest: selection of best-fit models of protein evolution. Bioinformatics 2005, 21, 2104–2105. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rambaut, A.; Drummond, A.J.; Xie, D.; Baele, G.; Suchard, M.A. Posterior summarisation in Bayesian phylogenetics using Tracer 1.7. Syst. Biol. 2018, 67, 901–904. [Google Scholar] [CrossRef] [PubMed]
- Rambaut, A. FigTree. 2013. Available online: http://tree.bio.ed.ac.uk/software/figtree (accessed on 12 June 2019).
- Yang, Z. PAML 4: Phylogenetic analysis by maximum likelihood. Mol. Biol. Evol. 2007, 24, 1586–1591. [Google Scholar] [CrossRef]
- Anisimova, M.; Yang, Z. Multiple hypothesis testing to detect lineages under positive selection that affects only a few sites. Mol. Biol. Evol. 2007, 24, 1219–1228. [Google Scholar] [CrossRef]
- Zhang, J.; Nielsen, R.; Yang, Z. Evaluation of an improved branch-site likelihood method for detecting positive selection at the molecular level. Mol. Biol. Evol. 2005, 22, 2472–2479. [Google Scholar] [CrossRef]
- Knudson, A.G. Mutation and cancer: statistical study of retinoblastoma. Proc. Natl. Acad. Sci. USA 1971, 68, 820–823. [Google Scholar] [CrossRef]
- Ruggieri, M.; Polizzi, A.; Spalice, A.; Salpietro, V.; Caltabiano, R.; D’Orazi, V.; Pavone, P.; Pirrone, C.; Magro, G.; Platania, N.; et al. The natural history of spinal neurofibromatosis: a critical review of clinical and genetic features. Clin. Genet. 2015, 87, 401–410. [Google Scholar] [CrossRef]
- Upadhyaya, M.; Huson, S.M.; Davies, M.; Thomas, N.; Chuzhanova, N.; Giovannini, S.; Evans, D.G.; Howard, E.; Kerr, B.; Griffiths, S.; et al. An absence of cutaneous neurofibromas associated with a 3-bp inframe deletion in exon 17 of the NF1 gene (c.2970-2972 delAAT): evidence of a clinically significant NF1 genotype-phenotype correlation. Am. J. Hum. Genet. 2007, 80, 140–151. [Google Scholar] [CrossRef]
- Rojnueangnit, K.; Xie, J.; Gomes, A.; Sharp, A.; Callens, T.; Chen, Y.; Liu, Y.; Cochran, M.; Abbott, M.A.; Atkin, J.; et al. High incidence of Noonan syndrome features including short stature and pulmonic stenosis in patients carrying NF1 missense mutations affecting p.Arg1809: genotype-phenotype correlation. Hum. Mutat. 2015, 36, 1052–1063. [Google Scholar] [CrossRef]
- Jenne, D.E.; Tinschert, S.; Reimann, H.; Lasinger, W.; Thiel, G.; Hameister, H.; Kehrer-Sawatzki, H. Molecular characterization and gene content of breakpoint boundaries in patients with neurofibromatosis type 1 with 17q11.2 microdeletions. Am. J. Hum. Genet. 2001, 69, 516–527. [Google Scholar] [CrossRef] [PubMed]
- López-Correa, C.; Dorschner, M.; Brems, H.; Lázaro, C.; Clementi, M.; Upadhyaya, M.; Dooijes, D.; Moog, U.; Kehrer-Sawatzki, H.; Rutkowski, J.L.; et al. Recombination hotspot in NF1 microdeletion patients. Hum. Mol. Genet. 2001, 10, 1387–1392. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Messiaen, L.; Vogt, J.; Bengesser, K.; Fu, C.; Mikhail, F.; Serra, E.; Garcia-Linares, C.; Cooper, D.N.; Lazaro, C.; Kehrer-Sawatzki, H. Mosaic type-1 NF1 microdeletions as a cause of both generalized and segmental neurofibromatosis type-1 (NF1). Hum. Mutat. 2011, 32, 213–219. [Google Scholar] [CrossRef] [PubMed]
- Hillmer, M.; Wagner, D.; Summerer, A.; Daiber, M.; Mautner, V.F.; Messiaen, L.; Cooper, D.N.; Kehrer-Sawatzki, H. Fine mapping of meiotic NAHR-associated crossovers causing large NF1 deletions. Hum. Mol. Genet. 2016, 25, 484–496. [Google Scholar] [CrossRef] [PubMed]
- Vogt, J.; Mussotter, T.; Bengesser, K.; Claes, K.; Högel, J.; Chuzhanova, N.; Fu, C.; van den Ende, J.; Mautner, V.F.; Cooper, D.N.; et al. Identification of recurrent type-2 NF1 microdeletions reveals a mitotic nonallelic homologous recombination hotspot underlying a human genomic disorder. Hum. Mutat. 2012, 33, 1599–1609. [Google Scholar] [CrossRef] [PubMed]
- Pasmant, E.; Sabbagh, A.; Spurlock, G.; Laurendeau, I.; Grillo, E.; Hamel, M.J.; Martin, L.; Barbarot, S.; Leheup, B.; Rodriguez, D.; et al. NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype. Hum Mutat 2010, 31, e1506–e1518. [Google Scholar] [CrossRef] [PubMed]
- Douglas, J.; Cilliers, D.; Coleman, K.; Tatton-Brown, K.; Barker, K.; Bernhard, B.; Burn, J.; Huson, S.; Josifova, D.; Lacombe, D.; et al. Mutations in RNF135, a gene within the NF1 microdeletion region, cause phenotypic abnormalities including overgrowth. Nat. Genet. 2007, 39, 963–965. [Google Scholar] [CrossRef]
- Nalepa, G.; Rolf, M.; Harper, Y.W. Drug discovery in the ubiquitin-proteasome system. Nat. Rev. Drug. Discov. 2006, 5, 596–613. [Google Scholar] [CrossRef]
- Squazzo, S.L.; O’Geen, H.; Komashko, V.M.; Krig, S.R.; Jin, V.X.; Jang, S.W.; Margueron, R.; Reinberg, D.; Green, R.; Farnham, P.J. Suz12 binds to silenced regions of the genome in a cell-type-specific manner. Genome Res. 2006, 16, 890–900. [Google Scholar] [CrossRef] [Green Version]
- Zhang, M.; Wang, Y.; Jones, S.; Sausen, M.; McMahon, K.; Sharma, R.; Wang, Q.; Belzberg, A.J.; Chaichana, K.; Gallia, G.L.; et al. Somatic mutations of SUZ12 in malignant peripheral nerve sheath tumors. Nat. Genet. 2014, 46, 1170–1172. [Google Scholar] [CrossRef]
- Di Croce, L.; Helin, K. Transcriptional regulation by Polycomb group proteins. Nat. Struct. Mol. Biol. 2013, 20, 1147–1155. [Google Scholar] [CrossRef] [PubMed]
- Asano, N.; Yoshida, A.; Ichikawa, H.; Mori, T.; Nakamura, M.; Kawai, A.; Hiraoka, N. Immunohistochemistry for trimethylated H3K27 in the diagnosis of malignant peripheral nerve sheath tumours. Histopathology 2017, 70, 385–393. [Google Scholar] [CrossRef] [PubMed]
- Huang, J.K.; Phillips, G.R.; Roth, A.D.; Pedraza, L.; Shan, W.; Belkaid, W.; Mi, S.; Fex-Svenningsen, A.; Florens, L.; Yates, J.R., 3rd; et al. Glial membranes at the node of Ranvier prevent neurite outgrowth. Science 2005, 310, 1813–1817. [Google Scholar] [CrossRef] [PubMed]
- Venturin, M.; Carra, S.; Gaudenzi, G.; Brunelli, S.; Gallo, G.R.; Moncini, S.; Cotelli, F.; Riva, P. ADAP2 in heart development: a candidate gene for the occurrence of cardiovascular malformations in NF1 microdeletion syndrome. J. Med. Genet. 2014, 51, 436–443. [Google Scholar] [CrossRef]
- Piddubnyak, V.; Rigou, P.; Michel, L.; Rain, J.C.; Geneste, O.; Wolkenstein, P.; Vidaud, D.; Hickman, J.A.; Mauviel, A.; Poyet, J.L. Positive regulation of apoptosis by HCA66, a new Apaf-1 interacting protein, and its putative role in the physiopathology of NF1 microdeletion syndrome patients. Cell Death Differ. 2007, 14, 1222–1233. [Google Scholar] [CrossRef]
- Lee, K.Y.; Fu, H.; Aladjem, M.I.; Myung, K. ATAD5 regulates the lifespan of DNA replication factories by modulating PCNA level on the chromatin. J. Cell Biol. 2013, 200, 31–44. [Google Scholar] [CrossRef]
- Bell, D.W.; Sikdar, N.; Lee, K.Y.; Price, J.C.; Chatterjee, R.; Park, H.D.; Fox, J.; Ishiai, M.; Rudd, M.L.; Pollock, L.M.; et al. Predisposition to cancer caused by genetic and functional defects of mammalian Atad5. PLoS Genet 2011, 7, e1002245. [Google Scholar] [CrossRef]
Gene Family | Model/Likelihood | Comparison | Parameters/Significance |
---|---|---|---|
CRLF3 | M0/-3789,882728 | M3 vs. M0 | 2ΔL = 31.37 (df = 4)/p << 0.001 * |
M1/-3774,195335 | M2 vs. M1 | 2ΔL = −6.51(df = 2)/p < 0.99 | |
M2/-3777,450354 | M8 vs. M7 | 2ΔL = 0.79(df = 2)/p < 0.5 | |
M3/-3774,195335 | |||
M7/-3774,904179 | |||
M8/-3774,50421 | |||
ATAD5 | M0/-22006,87329 | M3 vs. M0 | 2ΔL = 301.11 (df = 4)/p < 0.001 * |
M1/-21865,9053 | M2 vs. M1 | 2ΔL = 0 (df = 2)/p < 0.99 | |
M2/-21865,9053 | M8 vs. M7 | 2ΔL = 4.26 (df = 2)/p < 0.5 | |
M3/-21856,31708 | |||
M7/-21859,57933 | |||
M8/-21857,4487 | |||
ADAP2 | M0/-4320,93576 | M3 vs. M0 | 2ΔL = 83.94 (df = 4)/p < 0.001 * |
M1/-4283,476747 | M2 vs. M1 | 2ΔL = 0 (df = 2)/p < 0.99 | |
M2/-4283,476747 | M8 vs. M7 | 2ΔL = 0.176 (df = 2)/p < 0.99 | |
M3/-4278,962315 | |||
M7/-4279,346509 | |||
M8/-4279,258106 | |||
RNF135 | M0/-5802,616454 | M3 vs. M0 | 2ΔL = 116.5 (df = 4)/p < 0.001 * |
M1/-5745,76494 | M2 vs. M1 | 2ΔL = 2.80 (df = 2)/p < 0.1 | |
M2/-5744,363479 | M8 vs. M7 | 2ΔL = 11.65 (df = 2)/p < 0.005 * | |
M3/-5744,351541 | |||
M7/-5750,260024 | |||
M8/-5744,430178 | |||
NF1 | M0/-20275,12645 | M3 vs. M0 | 2ΔL = 73.08 (df = 4)/p < 0.001 * |
M1/-20240,46408 | M2 vs. M1 | 2ΔL = −4 × 10−6 (df = 2)/p < 0.99 | |
M2/-20240,46408 | M8 vs. M7 | 2ΔL = 1.57 (df = 2)/p < 0.99 | |
M3/-20238,58367 | M3 vs. M0 | ||
M7/-20239,50865 | |||
M8/-20238,71939 | |||
UTP6 | M0/-6507,150936 | M3 vs. M0 | 2ΔL = 154.60 (df = 4)/p < 0.001 * |
M1/-6433,008949 | M2 vs. M1 | 2ΔL = 0 (df = 2)/p < 0.99 | |
M2/-6433,008949 | M8 vs. M7 | 2ΔL = 8.52 (df = 2)/p < 0.025 * | |
M3/-6429,850049 | |||
M7/-6434,194703 | |||
M8/-6429,931052 | |||
SUZ12 | M0/-4810,097946 | M3 vs. M0 | 2ΔL = 14.64 (df = 4)/p < 0.005 * |
M1/-4803,610839 | M2 vs. M1 | 2ΔL = 0 (df = 2)/p < 0.99 | |
M2/-4803,610839 | M8 vs. M7 | 2ΔL = −0.000288 (df = 2)/p < 0.99 | |
M3/-4802,77363 | |||
M7/-4802,776934 | |||
M8/-4802,777078 | |||
OMG | M0/-3421,827547 | M3 vs. M0 | 2ΔL = 20.99 (df = 4)/p < 0.001 * |
M1/-3412,432711 | M2 vs. M1 | 2ΔL = 0 (df = 2)/p < 0.99 | |
M2/-3393,13422 | M8 vs. M7 | 2ΔL = 0.018 (df = 2)/p < 0.99 | |
M3/-3412,246309 | |||
M7/-3412,265355 | |||
M8/-3412,256186 | |||
LRRC37B | M0/-16071,4708 | M3 vs. M0 | 2ΔL = 120.7 (df = 4)/p < 0.001 * |
M1/-16018,91532 | M2 vs. M1 | 2ΔL = 9.87 (df = 2)/p < 0.005 * | |
M2/-16013,97878 | M8 vs. M7 | 2ΔL = 13.30 (df = 2)/p < 0.001 * | |
M3/-16011,07676 | |||
M7/-16018,02362 | |||
M8/-16011,36949 | |||
EVI2A | M0/-2792,694611 | M3 vs. M0 | 2ΔL = 44.45 (df = 4)/p < 0.001 * |
M1/-2771,253237 | M2 vs. M1 | 2ΔL = 1.32 (df = 2)/p < 0.99 | |
M2/-2770,590286 | M8 vs. M7 | 2ΔL = 4.28 (df = 2)/p < 0.1 | |
M3/-2770,464944 | |||
M7/-2772,654596 | |||
M8/-2770,510367 | |||
EVI2B | M0/-5998,097719 | M3 vs. M0 | 2ΔL = 71.86 (df = 4)/p < 0.001 * |
M1/-5964,792227 | M2 vs. M1 | 2ΔL = 1.85 (df = 2)/p < 0.1 | |
M2/-5963,862998 | M8 vs. M7 | 2ΔL = 6.25 (df = 2)/p < 0.025 * | |
M3/-5962,167576 | |||
M7/-5965,886294 | |||
M8/-5962,759212 | |||
RAB11FIP4 | M0/-8519,576811 | M3 vs. M0 | 2ΔL = 214.76 (df = 4)/p < 0.001 * |
M1/-8500,408316 | M2 vs. M1 | 2ΔL = 0 (df = 2)/p < 0.99 | |
M2/-8500,408316 | M8 vs. M7 | 2ΔL = 3.27 (df = 2)/p < 0.1 | |
M3/-8412,192643 | |||
M7/-8412,081211 | |||
M8/-8410,442254 | |||
TEFM | M0/-4523,914053 | M3 vs. M0 | 2ΔL = 95.54 (df = 4)/p < 0.001 * |
M1/-4479,041925 | M2 vs. M1 | 2ΔL = 2.70 (df = 2)/p < 0.1 | |
M2/-4477,690271 | M8 vs. M7 | 2ΔL = 3.91 (df = 2)/p < 0.1 | |
M3/-4476,141837 | |||
M7/-4478,690601 | |||
M8/-4476,734719 | |||
CORPS | M0/-2021,525059 | M3 vs. M0 | 2ΔL = 39.62 (df = 4)/p < 0.001 * |
M1/-2001,718453 | M2 vs. M1 | 2ΔL = 0 (df = 2/p < 0.99 | |
M2/-2001,718453 | M8 vs. M7 | 2ΔL = 0.26 (df = 2)/p < 0.5 | |
M3/-2001,71364 | |||
M7/-2001,856893 | |||
M8/-2001,724449 |
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Brussa Reis, L.; Turchetto-Zolet, A.C.; Fonini, M.; Ashton-Prolla, P.; Rosset, C. The Role of Co-Deleted Genes in Neurofibromatosis Type 1 Microdeletions: An Evolutive Approach. Genes 2019, 10, 839. https://doi.org/10.3390/genes10110839
Brussa Reis L, Turchetto-Zolet AC, Fonini M, Ashton-Prolla P, Rosset C. The Role of Co-Deleted Genes in Neurofibromatosis Type 1 Microdeletions: An Evolutive Approach. Genes. 2019; 10(11):839. https://doi.org/10.3390/genes10110839
Chicago/Turabian StyleBrussa Reis, Larissa, Andreia Carina Turchetto-Zolet, Maievi Fonini, Patricia Ashton-Prolla, and Clévia Rosset. 2019. "The Role of Co-Deleted Genes in Neurofibromatosis Type 1 Microdeletions: An Evolutive Approach" Genes 10, no. 11: 839. https://doi.org/10.3390/genes10110839
APA StyleBrussa Reis, L., Turchetto-Zolet, A. C., Fonini, M., Ashton-Prolla, P., & Rosset, C. (2019). The Role of Co-Deleted Genes in Neurofibromatosis Type 1 Microdeletions: An Evolutive Approach. Genes, 10(11), 839. https://doi.org/10.3390/genes10110839