REFERENCES
1. Friedman JM. Neurofibromatosis 1. In: Adam M, Ardinger H, et al., editors. Gene reviews. Seattle: University of Washington; 2019. p. 1-45. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1109/ [Last accessed on 21 Oct 2022].
2. Evans DG, Howard E, Giblin C, et al. Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am J Med Genet A 2010;152A:327-32.
3. Lammert M, Friedman JM, Kluwe L, Mautner VF. Prevalence of neurofibromatosis 1 in German children at elementary school enrollment. Arch Dermatol 2005;141:71-4.
4. Uusitalo E, Rantanen M, Kallionpää RA, et al. Distinctive cancer associations in patients with neurofibromatosis type 1. J Clin Oncol 2016;34:1978-86.
5. Yang FC, Chen S, Robling AG, et al. Hyperactivation of p21ras and PI3K cooperate to alter murine and human neurofibromatosis type 1-haploinsufficient osteoclast functions. J Clin Invest 2006;116:2880-91.
6. Rhodes SD, Yang H, Dong R, et al. Nf1 haploinsufficiency alters myeloid lineage commitment and function, leading to deranged skeletal homeostasis. J Bone Miner Res 2015;30:1840-51.
7. Zhu Y, Ghosh P, Charnay P, Burns DK, Parada LF. Neurofibromas in NF1: Schwann cell origin and role of tumor environment. Science 2002;296:920-2.
8. Liao CP, Booker RC, Brosseau JP, et al. Contributions of inflammation and tumor microenvironment to neurofibroma tumorigenesis. J Clin Invest 2018;128:2848-61.
9. Chen Z, Mo J, Brosseau JP, et al. Spatiotemporal loss of NF1 in Schwann Cell Lineage Leads to Different Types of Cutaneous Neurofibroma Susceptible to Modification by the Hippo Pathway. Cancer Discov 2019;9:114-29.
10. Stansfield BK, Bessler WK, Mali R, et al. Heterozygous inactivation of the Nf1 gene in myeloid cells enhances neointima formation via a rosuvastatin-sensitive cellular pathway. Hum Mol Genet 2013;22:977-88.
11. Lasater EA, Bessler WK, Mead LE, et al. Nf1+/- mice have increased neointima formation via hyperactivation of a Gleevec sensitive molecular pathway. Hum Mol Genet 2008;17:2336-44.
12. Li F, Downing BD, Smiley LC, et al. Neurofibromin-deficient myeloid cells are critical mediators of aneurysm formation in vivo. Circulation 2014;129:1213-24.
13. Silva AJ, Frankland PW, Marowitz Z, et al. A mouse model for the learning and memory deficits associated with neurofibromatosis type I. Nat Genet 1997;15:281-4.
14. Cui Y, Costa RM, Murphy GG, et al. Neurofibromin regulation of ERK signaling modulates GABA release and learning. Cell 2008;135:549-60.
15. Costa RM, Federov NB, Kogan JH, et al. Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature 2002;415:526-30.
16. Li W, Cui Y, Kushner SA, et al. The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1. Curr Biol 2005;15:1961-7.
17. Bajenaru ML, Zhu Y, Hedrick NM, Donahoe J, Parada LF, Gutmann DH. Astrocyte-specific inactivation of the neurofibromatosis 1 gene (NF1) is insufficient for astrocytoma formation. Mol Cell Biol 2002;22:5100-13.
18. Yap YS, McPherson JR, Ong CK, et al. The NF1 gene revisited - from bench to bedside. Oncotarget 2014;5:5873-92.
19. Hyman SL, Shores A, North KN. The nature and frequency of cognitive deficits in children with neurofibromatosis type 1. Neurology 2005;65:1037-44.
20. Akbarnia BA, Gabriel KR, Beckman E, Chalk D. Prevalence of scoliosis in neurofibromatosis. Spine 1992;17:S244-8.
21. Jaremko JL, MacMahon PJ, Torriani M, et al. Whole-body MRI in neurofibromatosis: incidental findings and prevalence of scoliosis. Skeletal Radiol 2012;41:917-23.
22. Holt JF. 1977 Edward B. D. Neuhauser lecture: neurofibromatosis in children. AJR Am J Roentgenol 1978;130:615-39.
23. Miller DT, Freedenberg D, Schorry E, Ullrich NJ, Viskochil D, Korf BR. Council on Genetics. Health supervision for children with neurofibromatosis type 1. Pediatrics 2019;143:e20190660.
24. Peltonen S, Pöyhönen M. Clinical diagnosis and atypical forms of NF1. In: Upadhyaya M, Cooper DN, editors. Neurofibromatosis type 1: molecular and cellular biology. Oxford: Bios Scientific; 2012. p. 17-30.
25. Mautner VF. Value of whole body MRI in patients with NF1. In: Upadhyaya M, Cooper DN, editors. Neurofibromatosis type 1: molecular and cellular biology. Oxford: Bios Scientific; 2012. p. 83-91.
27. Ferner RE. Clinical aspects of neurofibromatosis 1. In: Upadhyaya M, Cooper DN, editors. Neurofibromatosis type 1: from genotype to phenotype. Oxford: Bios Scientific; 1998. p. 21-38.
28. Easton DF, Ponder MA, Huson SM, Ponder BA. An analysis of variation in expression of neurofibromatosis (NF) type 1 (NF1): evidence for modifying genes. Am J Hum Genet 1993;53:305-13.
29. Rieley MB, Stevenson DA, Viskochil DH, Tinkle BT, Martin LJ, Schorry EK. Variable expression of neurofibromatosis 1 in monozygotic twins. Am J Med Genet A 2011;155A:478-85.
30. Messiaen L, Xie J. NF1 germline and somatic mosaicism. In: Upadhyaya M, Cooper D, editors. Neurofibromatosis type 1: molecular and cellular biology. Berlin Heidelberg: Springer-Verlag; 2012. p. 151-72.
31. García-Romero MT, Parkin P, Lara-Corrales I. Mosaic neurofibromatosis type 1: a systematic review. Pediatr Dermatol 2016;33:9-17.
32. Walker JA, Upadhyaya M. Emerging therapeutic targets for neurofibromatosis type 1. Expert Opin Ther Targets 2018;22:419-37.
33. Piovesan A, Antonaros F, Vitale L, Strippoli P, Pelleri MC, Caracausi M. Human protein-coding genes and gene feature statistics in 2019. BMC Res Notes 2019;12:315.
34. NCBI. Available from: https://www.ncbi.nlm.nih.gov/books/NBK7273/ [Last accessed on 21 Oct 2022].
35. Kehrer-Sawatzki H, Mautner VF, Cooper DN. Emerging genotype-phenotype relationships in patients with large NF1 deletions. Hum Genet 2017;136:349-76.
36. Danglot G, Régnier V, Fauvet D, Vassal G, Kujas M, Bernheim A. Neurofibromatosis 1 (NF1) mRNAs expressed in the central nervous system are differentially spliced in the 5’ part of the gene. Hum Mol Genet 1995;4:915-20.
37. Geist RT, Gutmann DH. Expression of a developmentally-regulated neuron-specific isoform of the neurofibromatosis 1 (NF1) gene. Neuroscience Letters 1996;211:85-8.
38. Kaufmann D, Müller R, Kenner O, et al. The N-terminal splice product NF1-10a-2 of the NF1 gene codes for a transmembrane segment. Biochem Biophys Res Commun 2002;294:496-503.
39. Nishi T, Lee PSY, Oka K, et al. Differential expression of two types of the neurofibromatosis type 1 ( NF1) gene transcripts related to neuronal differentiation. Oncogene 1991;1:1555-9.
40. Suzuki Y, Suzuki H, Kayama T, Yoshimoto T, Shibahara S. Brain tumors predominantly express the neurofibromatosis type 1 gene transcripts containing the 63 base insert in the region coding for GTPase activating protein-related domain. Biochem Biophys Res Commun 1991;181:955-61.
41. Gutmann D, Geist R, Wright D, Snider W. Expression of the neurofibromatosis 1 (NF1) isoforms in developing and adult rat tissues. Cell Growth Differ 1995;6:315-23.
42. Scheffzek K, Ahmadian MR, Wiesmüller L, et al. Structural analysis of the GAP-related domain from neurofibromin and its implications. EMBO J 1998;17:4313-27.
43. Ballester R, Marchuk D, Boguski M, et al. The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins. Cell 1990;63:851-9.
44. Martin GA, Viskoohil D, Bollag G, et al. The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21. Cell 1990;63:843-9.
45. Bos JL, Rehmann H, Wittinghofer A. GEFs and GAPs: critical elements in the control of small G proteins. Cell 2007;129:865-77.
46. Marchuk DA, Saulino AM, Tavakkol R, et al. cDNA cloning of the type 1 neurofibromatosis gene: complete sequence of the NF1 gene product. Genomics 1991;11:931-40.
47. Andersen LB, Ballester R, Marchuk DA, et al. A conserved alternative splice in the von Recklinghausen neurofibromatosis (NF1) gene produces two neurofibromin isoforms, both of which have GTPase-activating protein activity. Mol Cell Biol 1993;13:487-95.
48. Yunoue S, Tokuo H, Fukunaga K, et al. Neurofibromatosis type I tumor suppressor neurofibromin regulates neuronal differentiation via its GTPase-activating protein function toward Ras. J Biol Chem 2003;278:26958-69.
49. Daston MM, Ratner N. Neurofibromin, a predominantly neuronal GTPase activating protein in the adult, is ubiquitously expressed during development. Dev Dyn 1992;195:216-26.
50. Daston MM, Scrable H, Nordlund M, Sturbaum AK, Nissen LM, Ratner N. The protein product of the neurofibromatosis type 1 gene is expressed at highest abundance in neurons, Schwann cells, and oligodendrocytes. Neuron 1992;8:415-28.
51. Simanshu DK, Nissley DV, McCormick F. RAS proteins and their regulators in human disease. Cell 2017;170:17-33.
52. Stowe IB, Mercado EL, Stowe TR, et al. A shared molecular mechanism underlies the human rasopathies Legius syndrome and Neurofibromatosis-1. Genes Dev 2012;26:1421-6.
53. Sherekar M, Han SW, Ghirlando R, et al. Biochemical and structural analyses reveal that the tumor suppressor neurofibromin (NF1) forms a high-affinity dimer. J Biol Chem 2020;295:1105-19.
54. Naschberger A, Baradaran R, Rupp B, Carroni M. The structure of neurofibromin isoform 2 reveals different functional states. Nature 2021;599:315-9.
55. Brannan CI, Perkins AS, Vogel KS, et al. Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues. Genes Dev 1994;8:1019-29.
56. Jacks T, Shih TS, Schmitt EM, Bronson RT, Bernards A, Weinberg RA. Tumour predisposition in mice heterozygous for a targeted mutation in Nf1. Nat Genet 1994;7:353-61.
57. Wee P, Wang Z. Epidermal growth factor receptor cell proliferation signaling pathways. Cancers 2017;9:52.
58. Hobbs GA, Der CJ, Rossman KL. RAS isoforms and mutations in cancer at a glance. J Cell Sci 2016;129:1287-92.
60. Jindal GA, Goyal Y, Burdine RD, Rauen KA, Shvartsman SY. RASopathies: unraveling mechanisms with animal models. Dis Model Mech 2015;8:769-82.
61. Philpott C, Tovell H, Frayling IM, Cooper DN, Upadhyaya M. The NF1 somatic mutational landscape in sporadic human cancers. Hum Genomics 2017;11:13.
62. Wallace MD, Pfefferle AD, Shen L, et al. Comparative oncogenomics implicates the neurofibromin 1 gene (NF1) as a breast cancer driver. Genetics 2012;192:385-96.
63. See WL, Tan IL, Mukherjee J, Nicolaides T, Pieper RO. Sensitivity of glioblastomas to clinically available MEK inhibitors is defined by neurofibromin 1 deficiency. Cancer Res 2012;72:3350-9.
64. Lauchle JO, Kim D, Le DT, et al. Response and resistance to MEK inhibition in leukaemias initiated by hyperactive Ras. Nature 2009;461:411-4.
65. de Bruin EC, Cowell C, Warne PH, et al. Reduced NF1 expression confers resistance to EGFR inhibition in lung cancer. Cancer Discov 2014;4:606-19.
66. Py C, Christinat Y, Kreutzfeldt M, McKee TA, Dietrich PY, Tsantoulis P. Response of NF1-Mutated Melanoma to an MEK Inhibitor. JCO Precis Oncol 2018;2:1-11.
67. Byron SA, Tran NL, Halperin RF, et al. Prospective feasibility trial for genomics-informed treatment in recurrent and progressive glioblastoma. Clin Cancer Res 2018;24:295-305.
68. Omrani A, van der Vaart T, Mientjes E, et al. HCN channels are a novel therapeutic target for cognitive dysfunction in Neurofibromatosis type 1. Mol Psychiatry 2015;20:1311-21.
69. Tong J, Hannan F, Zhu Y, Bernards A, Zhong Y. Neurofibromin regulates G protein-stimulated adenylyl cyclase activity. Nat Neurosci 2002;5:95-6.
70. Guo HF, The I, Hannan F, Bernards A, Zhong Y. Requirement of Drosophila NF1 for activation of adenylyl cyclase by PACAP38-like neuropeptides. Science 1997;276:795-8.
71. Guo HF, Tong J, Hannan F, Luo L, Zhong Y. A neurofibromatosis-1-regulated pathway is required for learning in Drosophila. Nature 2000;403:895-8.
72. Hannan F, Ho I, Tong JJ, Zhu Y, Nurnberg P, Zhong Y. Effect of neurofibromatosis type I mutations on a novel pathway for adenylyl cyclase activation requiring neurofibromin and Ras. Hum Mol Genet 2006;15:1087-98.
73. Ho IS, Hannan F, Guo HF, Hakker I, Zhong Y. Distinct functional domains of neurofibromatosis type 1 regulate immediate versus long-term memory formation. J Neurosci 2007;27:6852-7.
74. Walker JA, Tchoudakova AV, McKenney PT, et al. Reduced growth of Drosophila neurofibromatosis 1 mutants reflects a non-cell-autonomous requirement for GTPase-Activating Protein activity in larval neurons. Genes Dev 2006;20:3311-23.
75. The I, Hannigan GE, Cowley GS, et al. Rescue of a Drosophila NF1 mutant phenotype by protein kinase A. Science 1997;276:791-4.
76. Hegedus B, Yeh TH, Lee DY, Emnett RJ, Li J, Gutmann DH. Neurofibromin regulates somatic growth through the hypothalamic-pituitary axis. Hum Mol Genet 2008;17:2956-66.
77. Szudek J, Birch P, Friedman JM. Growth in North American white children with neurofibromatosis 1 (NF1). J Med Genet 2000;37:933-8.
78. Elefteriou F, Kolanczyk M, Schindeler A, et al. Skeletal abnormalities in neurofibromatosis type 1: approaches to therapeutic options. Am J Med Genet A 2009;149A:2327-38.
79. Brown JA, Emnett RJ, White CR, et al. Reduced striatal dopamine underlies the attention system dysfunction in neurofibromatosis-1 mutant mice. Hum Mol Genet 2010;19:4515-28.
80. Diggs-Andrews KA, Tokuda K, Izumi Y, Zorumski CF, Wozniak DF, Gutmann DH. Dopamine deficiency underlies learning deficits in neurofibromatosis-1 mice. Ann Neurol 2013;73:309-15.
81. Patrakitkomjorn S, Kobayashi D, Morikawa T, et al. Neurofibromatosis type 1 (NF1) tumor suppressor, neurofibromin, regulates the neuronal differentiation of PC12 cells via its associating protein, CRMP-2. J Biol Chem 2008;283:9399-413.
82. Bellampalli SS, Khanna R. Towards a neurobiological understanding of pain in neurofibromatosis type 1: mechanisms and implications for treatment. Pain 2019;160:1007-18.
83. Fadhlullah SFB, Halim NBA, Yeo JYT, et al. Pathogenic mutations in neurofibromin identifies a leucine-rich domain regulating glioma cell invasiveness. Oncogene 2019;38:5367-80.
84. Shapira S, Barkan B, Friedman E, Kloog Y, Stein R. The tumor suppressor neurofibromin confers sensitivity to apoptosis by Ras-dependent and Ras-independent pathways. Cell Death Differ 2007;14:895-906.
85. Summers MA, Quinlan KG, Payne JM, Little DG, North KN, Schindeler A. Skeletal muscle and motor deficits in neurofibromatosis type 1. J Musculoskelet Neuronal Interact 2015;15:161-70.
86. Cornett KM, North KN, Rose KJ, Burns J. Muscle weakness in children with neurofibromatosis type 1. Dev Med Child Neurol 2015;57:733-6.
87. Pinho RS, Fusão EF, Paschoal JKSF, et al. Migraine is frequent in children and adolescents with neurofibromatosis type 1. Pediatr Int 2014;56:865-7.
88. Licis AK, Vallorani A, Gao F, et al. Prevalence of sleep disturbances in children with neurofibromatosis type 1. J Child Neurol 2013;28:1400-5.
89. Leschziner GD, Golding JF, Ferner RE. Sleep disturbance as part of the neurofibromatosis type 1 phenotype in adults. Am J Med Genet A 2013;161A:1319-22.
90. Lammert M, Friedman JM, Roth HJ, et al. Vitamin D deficiency associated with number of neurofibromas in neurofibromatosis 1. J Med Genet 2006;43:810-3.
91. Tucker T, Schnabel C, Hartmann M, et al. Bone health and fracture rate in individuals with neurofibromatosis 1 (NF1). J Med Genet 2009;46:259-65.
92. Stevenson DA, Viskochil DH, Carey JC, et al. Pediatric 25-hydroxyvitamin D concentrations in neurofibromatosis type 1. J Pediatr Endocrinol Metab 2011;24:169-74.
93. Souza Mario Bueno L, Rosset C, Aguiar E, et al. Vitamin D status and VDR genotype in NF1 patients: a case-control study from Southern Brazil. Int J Endocrinol 2015;2015:402838.
94. Hockett CW, Eelloo J, Huson SM, et al. Vitamin D status and muscle function in children with neurofibromatosis type 1 (NF1). J Musculoskelet Neuronal Interact 2013;13:111-9.
95. Jouhilahti EM, Peltonen S, Heape AM, Peltonen J. The pathoetiology of neurofibromatosis 1. Am J Pathol 2011;178:1932-9.
97. Zou MX, Butcher DT, Sadikovic B, Groves TC, Yee SP, Rodenhiser DI. Characterization of functional elements in the neurofibromatosis (NF1) proximal promoter region. Oncogene 2004;23:330-9.
98. Yang G, Khalaf W, van de Locht L, et al. Transcriptional repression of the Neurofibromatosis-1 tumor suppressor by the t(8;21) fusion protein. Mol Cell Biol 2005;25:5869-79.
99. Lu H, Liu P, Pang Q. MiR-27a-3p/miR-27b-3p promotes neurofibromatosis type 1 via targeting of NF1. J Mol Neurosci 2021;71:2353-63.
100. Cichowski K, Santiago S, Jardim M, Johnson BW, Jacks T. Dynamic regulation of the Ras pathway via proteolysis of the NF1 tumor suppressor. Genes Dev 2003;17:449-54.
101. McGillicuddy LT, Fromm JA, Hollstein PE, et al. Proteasomal and genetic inactivation of the NF1 tumor suppressor in gliomagenesis. Cancer Cell 2009;16:44-54.
102. Hollstein PE, Cichowski K. Identifying the Ubiquitin Ligase complex that regulates the NF1 tumor suppressor and Ras. Cancer Discov 2013;3:880-93.
103. Messiaen L, Wimmer K. NF1 mutational spectrum. In: Kaufmann D, editor. Neurofibromatoses. Basel: KARGER; 2008. p. 63-77.
104. Koczkowska M, Chen Y, Callens T, et al. Genotype-phenotype correlation in NF1: evidence for a more severe phenotype associated with missense mutations affecting NF1 codons 844-848. Am J Hum Genet 2018;102:69-87.
105. Valero MC, Martín Y, Hernández-Imaz E, et al. A highly sensitive genetic protocol to detect NF1 mutations. J Mol Diagn 2011;13:113-22.
106. Kurosaki T, Popp MW, Maquat LE. Quality and quantity control of gene expression by nonsense-mediated mRNA decay. Nat Rev Mol Cell Biol 2019;20:406-20.
107. Ben-Shachar S, Constantini S, Hallevi H, et al. Increased rate of missense/in-frame mutations in individuals with NF1-related pulmonary stenosis: a novel genotype-phenotype correlation. Eur J Hum Genet 2013;21:535-9.
108. Ruggieri M, Polizzi A, Spalice A, et al. The natural history of spinal neurofibromatosis: a critical review of clinical and genetic features. Clin Genet 2015;87:401-10.
109. Martin MC, Zeng G, Yu J, Schiltz GE. Small molecule approaches for targeting the polycomb repressive complex 2 (PRC2) in cancer. J Med Chem 2020;63:15344-70.
110. Young L, Huang Z, Han S, et al. Severe phenotype-linked NF1 substitution mutations in codons 844-848 of neurofibromin act in a dominant negative manner by destabilizing wild-type protein. In: NF Conference Book. Children’s Tumor Foundation; 2020. p. 23. Available from: https://www.ctf.org/images/uploads/documents/2020_NF_Conference_Book.pdf [Last accessed on 21 Oct 2022].
111. Long A, Liu H, Liu J, et al. Analysis of patient-specific NF1 variants leads to functional insights for Ras signaling that can impact personalized medicine. Hum Mutat 2022;43:30-41.
112. Pasmant E, Sabbagh A, Spurlock G, et al. Members of the NF France Network. NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype. Hum Mutat 2010;31:E1506-18.
113. Barrea C, Vaessen S, Bulk S, Harvengt J, Misson JP. Phenotype-genotype correlation in children with neurofibromatosis type 1. Neuropediatrics 2018;49:180-4.
114. Koczkowska M, Callens T, Chen Y, et al. Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype-phenotype study in neurofibromatosis type 1. Hum Mutat 2020;41:299-315.
115. Upadhyaya M, Huson SM, Davies M, 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;80:140-51.
116. Koczkowska M, Callens T, Gomes A, et al. Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype-phenotype correlation. Genet Med 2019;21:867-76.
117. Rojnueangnit K, Xie J, Gomes A, 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;36:1052-63.
118. Knudson AG Jr. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A 1971;68:820-3.
119. Mellert K, Lechner S, Lüdeke M, et al. Restoring functional neurofibromin by protein transduction. Sci Rep 2018;8:6171.
120. Lasater EA, Li F, Bessler WK, et al. Genetic and cellular evidence of vascular inflammation in neurofibromin-deficient mice and humans. J Clin Invest 2010;120:859-70.
121. Stevenson DA, Elefteriou F. Molecular basis of bone abnormalities in NF1. In: Upadhyaya M, Cooper DN, editors. Molecular and cellular biology of neurofibromatosis type 1. Heidelberg: Springer Verlag; 2012. p. 327-40. Available from: https://link.springer.com/book/10.1007/978-3-642-32864-0 [Last accessed on 21 Oct 2022].
122. Stansfield BK, Ingram DA, Conway SJ, Friedman JM. Molecular basis of cardiovascular abnormalities in NF1. In: Upadhyaya M, Cooper DN, editors. Molecular and cellular biology of neurofibromatosis type 1. Heidelberg: Springer Verlag; 2012. p. 353-66. Available from: https://link.springer.com/book/10.1007/978-3-642-32864-0 [Last accessed on 21 Oct 2022].
123. Yu X, Chen S, Potter OL, et al. Neurofibromin and its inactivation of Ras are prerequisites for osteoblast functioning. Bone 2005;36:793-802.
124. Stevenson DA, Schwarz EL, Viskochil DH, et al. Evidence of increased bone resorption in neurofibromatosis type 1 using urinary pyridinium crosslink analysis. Pediatr Res 2008;63:697-701.
125. Schindeler A, Morse A, Harry L, et al. Models of tibial fracture healing in normal and Nf1-deficient mice. J Orthop Res 2008;26:1053-60.
126. Schindeler A, Birke O, Yu NY, et al. Distal tibial fracture repair in a neurofibromatosis type 1-deficient mouse treated with recombinant bone morphogenetic protein and a bisphosphonate. J Bone Joint Surg Br 2011;93:1134-9.
127. Rasmussen SA, Yang Q, Friedman JM. Mortality in neurofibromatosis 1: an analysis using U.S. death certificates. Am J Hum Genet 2001;68:1110-8.
128. Friedman JM, Arbiser J, Epstein JA, et al. Cardiovascular disease in neurofibromatosis 1: report of the NF1 Cardiovascular Task Force. Genet Med 2002;4:105-11.
129. Oderich GS, Sullivan TM, Bower TC, et al. Vascular abnormalities in patients with neurofibromatosis syndrome type I: clinical spectrum, management, and results. J Vasc Surg 2007;46:475-84.
130. Anastasaki C, Woo AS, Messiaen LM, Gutmann DH. Elucidating the impact of neurofibromatosis-1 germline mutations on neurofibromin function and dopamine-based learning. Hum Mol Genet 2015;24:3518-28.
131. Jentarra GM, Rice SG, Olfers S, Rajan C, Saffen DM, Narayanan V. Skewed allele-specific expression of the NF1 gene in normal subjects: a possible mechanism for phenotypic variability in neurofibromatosis type 1. J Child Neurol 2012;27:695-702.
132. Hoffmeyer S, Assum G, Griesser J, Kaufmann D, Nürnberg P, Krone W. On unequal allelic expression of the neurofibromin gene in neurofibromatosis type 1. Hum Mol Genet 1995;4:1267-72.
133. Molosh AI, Johnson PL, Spence JP, et al. Social learning and amygdala disruptions in Nf1 mice are rescued by blocking p21-activated kinase. Nat Neurosci 2014;17:1583-90.
134. Yang FC, Ingram DA, Chen S, et al. Neurofibromin-deficient Schwann cells secrete a potent migratory stimulus for Nf1+/- mast cells. J Clin Invest 2003;112:1851-61.
135. Yang FC, Ingram DA, Chen S, et al. Nf1-dependent tumors require a microenvironment containing Nf1+/- and c-kit-dependent bone marrow. Cell 2008;135:437-48.
136. Bajenaru ML, Hernandez MR, Perry A, et al. Optic nerve glioma in mice requires astrocyte Nf1 gene inactivation and Nf1 brain heterozygosity. Cancer Res 2003;63:8573-7.
137. Radomska KJ, Coulpier F, Gresset A, et al. Cellular origin, tumor progression, and pathogenic mechanisms of cutaneous neurofibromas revealed by mice with Nf1 knockout in boundary cap cells. Cancer Discov 2019;9:130-47.
138. Brosseau JP, Liao CP, Wang Y, et al. NF1 heterozygosity fosters de novo tumorigenesis but impairs malignant transformation. Nat Commun 2018;9:5014.
139. Kehrer-Sawatzki H, Bengesser K, Callens T, et al. Identification of large NF1 duplications reciprocal to NAHR-mediated type-1 NF1 deletions. Hum Mutat 2014;35:1469-75.
140. Moles KJ, Gowans GC, Gedela S, et al. NF1 microduplications: identification of seven nonrelated individuals provides further characterization of the phenotype. Genet Med 2012;14:508-14.
141. Grisart B, Rack K, Vidrequin S, et al. NF1 microduplication first clinical report: association with mild mental retardation, early onset of baldness and dental enamel hypoplasia? Eur J Hum Genet 2008;16:305-11.
142. Umanoff H, Edelmann W, Pellicer A, Kucherlapati R. The murine N-ras gene is not essential for growth and development. Proc Natl Acad Sci U S A 1995;92:1709-13.
143. Esteban LM, Vicario-Abejón C, Fernández-Salguero P, et al. Targeted genomic disruption of H-ras and N-ras, individually or in combination, reveals the dispensability of both loci for mouse growth and development. Mol Cell Biol 2001;21:1444-52.
144. Koera K, Nakamura K, Nakao K, et al. K-ras is essential for the development of the mouse embryo. Oncogene 1997;15:1151-9.
145. Nakamura K, Ichise H, Nakao K, et al. Partial functional overlap of the three ras genes in mouse embryonic development. Oncogene 2008;27:2961-8.
146. Matharu N, Rattanasopha S, Tamura S, et al. CRISPR-mediated activation of a promoter or enhancer rescues obesity caused by haploinsufficiency. Science 2019;363:eaau0629.
147. Dang VT, Kassahn KS, Marcos AE, Ragan MA. Identification of human haploinsufficient genes and their genomic proximity to segmental duplications. Eur J Hum Genet 2008;16:1350-7.
148. Delaney JR, Patel CB, Willis KM, et al. Haploinsufficiency networks identify targetable patterns of allelic deficiency in low mutation ovarian cancer. Nat Commun 2017;8:14423.
149. Leen WG, Klepper J, Verbeek MM, et al. Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder. Brain 2010;133:655-70.
150. Tang M, Park SH, De Vivo DC, Monani UR. Therapeutic strategies for glucose transporter 1 deficiency syndrome. Ann Clin Transl Neurol 2019;6:1923-32.
151. Brunklaus A, Zuberi SM. Dravet syndrome--from epileptic encephalopathy to channelopathy. Epilepsia 2014;55:979-84.
152. Rabiee B, Anwar KN, Shen X, et al. Gene dosage manipulation alleviates manifestations of hereditary PAX6 haploinsufficiency in mice. Sci Transl Med 2020;12:eaaz4894.
153. Tang M, Gao G, Rueda CB, et al. Brain microvasculature defects and Glut1 deficiency syndrome averted by early repletion of the glucose transporter-1 protein. Nat Commun 2017;8:14152.
154. Colasante G, Lignani G, Brusco S, et al. dCas9-based scn1a gene activation restores inhibitory interneuron excitability and attenuates seizures in dravet syndrome mice. Mol Ther 2020;28:235-53.
155. Huang HS, Allen JA, Mabb AM, et al. Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. Nature 2011;481:185-9.
156. Hasson SA, Fogel AI, Wang C, et al. Chemogenomic profiling of endogenous PARK2 expression using a genome-edited coincidence reporter. ACS Chem Biol 2015;10:1188-97.
157. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001;46:3-26.
158. Leeson PD, Springthorpe B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nat Rev Drug Discov 2007;6:881-90.
159. Li Q, Kang C. Mechanisms of action for small molecules revealed by structural biology in drug discovery. Int J Mol Sci 2020;21:5262.
161. Sun W, Zheng W, Simeonov A. Drug discovery and development for rare genetic disorders. Am J Med Genet A 2017;173:2307-22.
163. Middleton PG, Mall MA, Dřevínek P, et al. VX17-445-102 Study Group. Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single phe508del allele. N Engl J Med 2019;381:1809-19.
164. Zhu PJ, Khatiwada S, Cui Y, et al. Activation of the ISR mediates the behavioral and neurophysiological abnormalities in Down syndrome. Science 2019;366:843-9.
165. Porter BA, Ortiz MA, Bratslavsky G, Kotula L. Structure and function of the nuclear receptor superfamily and current targeted therapies of prostate cancer. Cancers 2019;11:1852.
166. Zheng XS, Chan T-F, Zhou HH. Genetic and genomic approaches to identify and study the targets of bioactive small molecules. Chem Biol 2004;11:609-18.
167. Huynh DP, Nechiporuk T, Pulst SM. Differential expression and tissue distribution of type I and type II neurofibromins during mouse fetal development. Dev Biol 1994;161:538-51.
168. Gutmann DH, Cole JL, Collins FS. Chapter 33 Expression of the neurofibromatosis type 1 (NF1) gene during mouse embryonic development. Gene expression in the central nervous system. Elsevier; 1995. p. 327-35.
169. Sherman L, Daston M, Ratner N. Neurofibromin: distribution, cell biology and role in neurofibromatosis type 1. In: Upadhyaya M, Cooper D, editors. Neurofibromatosis type 1 from genotype to phenotype. Oxford: Bios scientific; 1998. p. 113-26.
170. Ratner N, Miller SJ. A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor. Nat Rev Cancer 2015;15:290-301.
172. Patel A, Zhao J, Duan D, Lai Y. Design of AAV vectors for delivery of large or multiple transgenes. Methods Mol Biol 2019;1950:19-33.
173. Trapani I. Adeno-associated viral vectors as a tool for large gene delivery to the retina. Genes 2019;10:287.
174. Bai RY, Esposito D, Tam AJ, et al. Feasibility of using NF1-GRD and AAV for gene replacement therapy in NF1-associated tumors. Gene Ther 2019;26:277-86.
176. Gross AM, Wolters PL, Dombi E, et al. Selumetinib in children with inoperable plexiform neurofibromas. N Engl J Med 2020;382:1430-42.