Neurofibromatosis type 1 pathophysiology: Difference between revisions

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{{Neurofibromatosis type 1}}
{{Neurofibromatosis type 1}}


{{CMG}}; {{AE}}  
{{CMG}}; {{AE}}[[User:MoisesRomo|Moises Romo M.D.]]
==Overview==
==Overview==
The exact pathogenesis of [disease name] is not fully understood.
'''[[Neurofibromatosis type 1]]''' is an [[Autosomal chromosome|autosomal]] [[syndrome]] caused by a [[mutation]] in [[gene]] [[NF1]] of [[chromosome 17]], wich leads to a [[Defective interfering particle|defective]] [[neurofibromin 1]] [[protein]]. This [[mutation]] constitutes a phenotype with very [[pathognomonic]] features that are not always present; among them are the presence of [[Lisch nodule]]<nowiki/>s, [[Neurofibroma|neurofibromas]], [[scoliosis]], [[cognitive disabilities]], [[vision]] disorders, multiple [[Café au lait spot|café au lait spots]] and [[epilepsy]].
<br />
==Normal physiology==


OR
* [[Neurofibromin 1|Neurofibromin 1 (''NF1)'']] [[gene]], is  a large multi-domain protein, of approximately 250 KDa, containing 2,818 [[amino acids]],<ref name="pmid26860753">{{cite journal |vauthors=Rad E, Tee AR |title=Neurofibromatosis type 1: Fundamental insights into cell signalling and cancer |journal=Semin. Cell Dev. Biol. |volume=52 |issue= |pages=39–46 |date=April 2016 |pmid=26860753 |doi=10.1016/j.semcdb.2016.02.007 |url=}}</ref><ref name="pmid23257896">{{cite journal |vauthors=Seminog OO, Goldacre MJ |title=Risk of benign tumours of nervous system, and of malignant neoplasms, in people with neurofibromatosis: population-based record-linkage study |journal=Br. J. Cancer |volume=108 |issue=1 |pages=193–8 |date=January 2013 |pmid=23257896 |pmc=3553528 |doi=10.1038/bjc.2012.535 |url=}}</ref> located in [[chromosome 17]],<ref name="UpadhyayaCooper2012">{{cite journal|last1=Upadhyaya|first1=Meena|last2=Cooper|first2=David N.|year=2012|doi=10.1007/978-3-642-32864-0}}</ref> codes for the [[GTPase activating protein|GTPase-activating protein]], [[neurofibromin]].<ref name="pmid27622733">{{cite journal |vauthors=Peltonen S, Kallionpää RA, Peltonen J |title=Neurofibromatosis type 1 (NF1) gene: Beyond café au lait spots and dermal neurofibromas |journal=Exp. Dermatol. |volume=26 |issue=7 |pages=645–648 |date=July 2017 |pmid=27622733 |doi=10.1111/exd.13212 |url=}}</ref><ref name="pmid16813595">{{cite journal |vauthors=Trovó-Marqui AB, Tajara EH |title=Neurofibromin: a general outlook |journal=Clin. Genet. |volume=70 |issue=1 |pages=1–13 |date=July 2006 |pmid=16813595 |doi=10.1111/j.1399-0004.2006.00639.x |url=}}</ref> This [[protein]], is a [[Tumor suppressor gene|tumor suppressor]] expressed in many [[Cell (biology)|cells]], primarily in [[neurons]], [[Glial cells|glial]], [[immune cells]], [[Endothelial cells|endothelial cellls]] of the [[adrenal medulla]], [[Schwann cells]] and early in [[melanocyte]] development.<ref name="pmid19539839">{{cite journal |vauthors=Boyd KP, Korf BR, Theos A |title=Neurofibromatosis type 1 |journal=J. Am. Acad. Dermatol. |volume=61 |issue=1 |pages=1–14; quiz 15–6 |date=July 2009 |pmid=19539839 |pmc=2716546 |doi=10.1016/j.jaad.2008.12.051 |url=}}</ref><ref name="pmid28230061">{{cite journal |vauthors=Gutmann DH, Ferner RE, Listernick RH, Korf BR, Wolters PL, Johnson KJ |title=Neurofibromatosis type 1 |journal=Nat Rev Dis Primers |volume=3 |issue= |pages=17004 |date=February 2017 |pmid=28230061 |doi=10.1038/nrdp.2017.4 |url=}}</ref>
* [[Neurofibromin]] works by downregulating the RAS/MAPK pathway, by accelerating [[hydrolisis]] and preventing [[cell proliferation]].<ref name="pmid16813595" /><ref name="pmid19539839" /> <ref name="HarrisinghLloyd2014">{{cite journal|last1=Harrisingh|first1=Marie C.|last2=Lloyd|first2=Alison C.|title=Ras/Raf/ERK signalling and NF1: Implications for Neurofibroma Formation|journal=Cell Cycle|volume=3|issue=10|year=2014|pages=1255–1258|issn=1538-4101|doi=10.4161/cc.3.10.1182}}</ref><ref name="WangKim2012">{{cite journal|last1=Wang|first1=Yuan|last2=Kim|first2=Edward|last3=Wang|first3=Xiaojing|last4=Novitch|first4=Bennett G.|last5=Yoshikawa|first5=Kazuaki|last6=Chang|first6=Long-Sheng|last7=Zhu|first7=Yuan|title=ERK Inhibition Rescues Defects in Fate Specification of Nf1-Deficient Neural Progenitors and Brain Abnormalities|journal=Cell|volume=150|issue=4|year=2012|pages=816–830|issn=00928674|doi=10.1016/j.cell.2012.06.034}}</ref>
* [[Neurofibromin]] interacts cytoskeletal [[Microtubules|microtubular]] and [[Microfilament|microfilaments]] for proper [[neuronal]] development.<ref name="pmid26860753" /><ref name="pmid24931163">{{cite journal |vauthors=Dodd KM, Yang J, Shen MH, Sampson JR, Tee AR |title=mTORC1 drives HIF-1α and VEGF-A signalling via multiple mechanisms involving 4E-BP1, S6K1 and STAT3 |journal=Oncogene |volume=34 |issue=17 |pages=2239–50 |date=April 2015 |pmid=24931163 |pmc=4172452 |doi=10.1038/onc.2014.164 |url=}}</ref> <br />


It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
==Pathogenesis and genetics==


OR
* [[Neurofibromatosis type 1]] is an autosomal syndrome, although, roughly 50% of [[gene]] [[Mutation|mutations]] arise from [[de novo]] events.<ref name="pmid26860753" />
* The large size of the [[NF1|NF1 gene]] (350 kb with 60 exons) predisposes to a high [[mutation]] rate, with approximately one [[mutation]] occurring per 10,000 gametes.<ref name="pmid10862084">{{cite journal |vauthors=Messiaen LM, Callens T, Mortier G, Beysen D, Vandenbroucke I, Van Roy N, Speleman F, Paepe AD |title=Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects |journal=Hum. Mutat. |volume=15 |issue=6 |pages=541–55 |date=2000 |pmid=10862084 |doi=10.1002/1098-1004(200006)15:6<541::AID-HUMU6>3.0.CO;2-N |url=}}</ref>
* [[NF1]] mutations lead to [[protein]] truncation (loss of [[neurofibromin]] [[Gene expression|expression]]), which in turn produces increased [[cell growth]] and survival through expression of [[RAS]] to ultimately increase chances for [[malignant transformation]].<ref name="pmid28230061" /><ref name="pmid1946460">{{cite journal |vauthors=DeClue JE, Cohen BD, Lowy DR |title=Identification and characterization of the neurofibromatosis type 1 protein product |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=88 |issue=22 |pages=9914–8 |date=November 1991 |pmid=1946460 |pmc=52837 |doi=10.1073/pnas.88.22.9914 |url=}}</ref><ref name="pmid26860753" />
* More than 3,000 [[NF1|NF1 gene]] mutations have been recognised.<ref name="pmid28230061" />
* Loss of [[neurofibromin]] leads to formation of [[Skin lesion|skin lesions]], [[tumours]] and skeletal abnormalities.<ref name="pmid28230061" />
* Patients with [[neurofibromatosis type 1]] syndrome have a higher incidence of GI, [[liver]], [[lung]], [[bone]], [[thyroid]], [[breast]] and [[ovarian]] [[Cancer|cancers]].<ref name="pmid26860753" /><ref name="pmid15683544">{{cite journal |vauthors=Friedrich RE, Schmelzle R, Hartmann M, Fünsterer C, Mautner VF |title=Resection of small plexiform neurofibromas in neurofibromatosis type 1 children |journal=World J Surg Oncol |volume=3 |issue=1 |pages=6 |date=January 2005 |pmid=15683544 |pmc=549083 |doi=10.1186/1477-7819-3-6 |url=}}</ref>
* [[Nerve sheath tumor|Nerve sheath tumours]] can arise from benign [[Neurofibroma|neurofibromas]] and these compose the first cause of death in individuals with [[neurofibromatosis type 1]].<ref name="pmid26860753" />
* Patients with [[neurofibromatosis type 1]] can present a wide variability of clinical features, even in the same family since mutation mechanisms are so vast. Interestingly, patients can present traits limited to a part of their body ([[Mosaic (genetics)|mosaicism]]).<ref name="pmid28230061" />
* Therapies are focused to inhibit [[RAS]] [[phenylation]] to block [[oncogenic]] [[RAS]] signalling.<ref name="pmid26860753" /> <br />


[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
==Associated conditions==


OR
*[[Neurofibromatosis type 2]] is a [[genetic]] condition which may be inherited or may arise spontaneously. It is caused by [[NF2 gene]]([[Merlin (protein)|Merlin]] gene) mutation in [[chromosome 22]] and presents with bilateral [[Vestibular system|vestibular]] schwannomas([[Acoustic neuroma|acoustic neuromas]]).<ref name="urlNeurofibromatosis type II - Wikipedia">{{cite web |url=https://en.wikipedia.org/wiki/Neurofibromatosis_type_II |title=Neurofibromatosis type II - Wikipedia |format= |work= |accessdate=}}</ref>
*[[Neurofibromatosis type 1]] is part of the group of [[Neurocutaneous syndrome|neurocutaneous]] disorders called [[phakomatoses]], some of the most famous conditions from this group are:
**[[Tuberous sclerosis]]
**[[Sturge-Weber disease|Sturge-Weber]]
**[[Von Hippel-Lindau disease]]
**[[Ataxia telangiectasia]]


Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
<br />
==Gross pathology==


OR
* The most common non-­neoplastic manifestations are [[Café au lait spot|cafe-au-lait]] macules, which is a very sensitive finding when they appear in large quantities.<ref name="pmid28230061" /><ref name="pmid17914445">{{cite journal |vauthors=De Schepper S, Maertens O, Callens T, Naeyaert JM, Lambert J, Messiaen L |title=Somatic mutation analysis in NF1 café au lait spots reveals two NF1 hits in the melanocytes |journal=J. Invest. Dermatol. |volume=128 |issue=4 |pages=1050–3 |date=April 2008 |pmid=17914445 |doi=10.1038/sj.jid.5701095 |url=}}</ref><ref name="pmid29478615">{{cite journal |vauthors=Cimino PJ, Gutmann DH |title=Neurofibromatosis type 1 |journal=Handb Clin Neurol |volume=148 |issue= |pages=799–811 |date=2018 |pmid=29478615 |doi=10.1016/B978-0-444-64076-5.00051-X |url=}}</ref>
* [[Dysplasia]] of the [[Long bone|long bones]] and sphenoid wings, [[fractures]], and [[pseudoarthrosis]] are common findings in patients with [[neurofibromatosis type 1]].<ref name="pmid29478615" /><ref name="urlClinical and genetic patterns of neurofibromatosis 1 and 2. | British Journal of Ophthalmology">{{cite web |url=https://bjo.bmj.com/content/77/10/662 |title=Clinical and genetic patterns of neurofibromatosis 1 and 2. &#124; British Journal of Ophthalmology |format= |work= |accessdate=}}</ref> They occur due to osteoblastic and osteoclastic dysfunction which lead to decreased [[Mineralization (biology)|mineralization]].<ref name="pmid28230061" />
* The defects in [[bone]] observed in individuals with [[neurofibromatosis type 1]] are due to the loss of both copies of [[NF1]] in [[osteoclasts]] and/or [[Osteoblast|osteoblasts]].Osteoblast dysfunction following [[NF1]] loss results in an increased generation of [[Pyrophosphatase|pyrophosphat]]<nowiki/>e, which inhibits bone mineral ([[Hydroxylapatite|hydroxyapatite]]) production and bone [[mineralization]], causing reduced bone [[density]] and a higher risk of bone [[Fracture (bone)|fracture]].<ref name="pmid28230061" /><ref>{{cite journal|doi=10.1016/j.jpeds.2006.10.048Get rights and content Objective}}</ref>
* [[Lisch nodules]] are [[hyperpigmented]] [[hamartomas]] of the [[Iris (eye)|iris]], which are seen in 95–100% of adults with [[neurofibromatosis type 1]].<ref name="pmid29478615" /><ref name="urlClinical and genetic patterns of neurofibromatosis 1 and 2. | British Journal of Ophthalmology" />
* [[Neurofibroma|Neurofibromas]] are benign [[Peripheral nervous system|peripheral]] [[Nerve sheath tumor|nerve sheath tumors]] that arise from [[Schwann cells]], and represent the most frequent type of [[tumors]] in patients with [[Neurofibromatosis type 1|neurofibromatosis type 1;]] they can be divided as dermal and plexiform neurofibromas.<ref name="pmid28230061" /><ref name="pmid22327363">{{cite journal |vauthors=Rodriguez FJ, Folpe AL, Giannini C, Perry A |title=Pathology of peripheral nerve sheath tumors: diagnostic overview and update on selected diagnostic problems |journal=Acta Neuropathol. |volume=123 |issue=3 |pages=295–319 |date=March 2012 |pmid=22327363 |pmc=3629555 |doi=10.1007/s00401-012-0954-z |url=}}</ref>
* [[Optic gliomas]] are the most common brain tumors in [[neurofibromatosis type 1]], they are observed in 15–20% of children younger than 7 years.<ref name="pmid29478615" /><ref name="LewisGerson1984">{{cite journal|last1=Lewis|first1=Richard Alan|last2=Gerson|first2=L. Paul|last3=Axelson|first3=Kenneth A.|last4=Riccardi|first4=Vincent M.|last5=Whitford|first5=Randolph P.|title=von Recklinghausen Neurofibromatosis|journal=Ophthalmology|volume=91|issue=8|year=1984|pages=929–935|issn=01616420|doi=10.1016/S0161-6420(84)34217-8}}</ref>
* Several types of [[cerebrovascular disease]], including stenotic or occlusive disease, vascular dilatation or [[aneurysm]], [[arteriovenous fistula]], [[Moyamoya disease|moyamoya syndrome]], or [[vascular]] proliferation have been consistently found in [[biopsies]] of patients with [[neurofibromatosis type 1]].<ref name="pmid29478615" /><ref name="RosserVezina2005">{{cite journal|last1=Rosser|first1=T. L.|last2=Vezina|first2=G.|last3=Packer|first3=R. J.|title=Cerebrovascular abnormalities in a population of children with neurofibromatosis type 1|journal=Neurology|volume=64|issue=3|year=2005|pages=553–555|issn=0028-3878|doi=10.1212/01.WNL.0000150544.00016.69}}</ref> <br />


==Microscopic pathology==


[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
* [[Cafe au lait Spot|Cafe au-lait]] macules consist of a dense [[population]] of [[melanocytes]] with [[biallelic]] [[NF1]] [[inactivation]].<ref name="pmid28230061" /><ref name="pmid17914445" />
 
* [[Neurofibroma|Neurofibromas]] are benign [[Peripheral nervous system|peripheral]] [[Nerve sheath tumor|nerve sheath tumors]] composed of [[neoplastic]] [[Schwann cells]], [[fibroblasts]], [[Blood vessel|blood vessels]], and [[mast cells]].<ref name="pmid29478615" />
OR
* [[Optic nerve glioma|Optic pathway gliomas]] are composed of [[astrocytes]], [[oligodendrocytes]], [[neurons]], [[Microglial cell|microglia]] and progenitor or [[stem cells]].<ref name="pmid28230061" /><ref name="pmid14695164">{{cite journal |vauthors=Bajenaru ML, Hernandez MR, Perry A, Zhu Y, Parada LF, Garbow JR, Gutmann DH |title=Optic nerve glioma in mice requires astrocyte Nf1 gene inactivation and Nf1 brain heterozygosity |journal=Cancer Res. |volume=63 |issue=24 |pages=8573–7 |date=December 2003 |pmid=14695164 |doi= |url=}}</ref> <br />
 
The progression to [disease name] usually involves the [molecular pathway].
 
OR
 
The pathophysiology of [disease/malignancy] depends on the histological subtype.
 
==Pathophysiology==
===Physiology===
The normal physiology of [name of process] can be understood as follows:
 
===Pathogenesis===
*The exact pathogenesis of [disease name] is not completely understood.
OR
*It is understood that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
*[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
*Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
*[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
*The progression to [disease name] usually involves the [molecular pathway].
*The pathophysiology of [disease/malignancy] depends on the histological subtype.
 
==Genetics==
[Disease name] is transmitted in [mode of genetic transmission] pattern.
 
OR
 
Genes involved in the pathogenesis of [disease name] include:
*[Gene1]
*[Gene2]
*[Gene3]
 
OR
 
The development of [disease name] is the result of multiple genetic mutations such as:
 
*[Mutation 1]
*[Mutation 2]
*[Mutation 3]
 
==Associated Conditions==
Conditions associated with [disease name] include:
 
*[Condition 1]
*[Condition 2]
*[Condition 3]
 
==Gross Pathology==
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
 
==Microscopic Pathology==
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].


==References==
==References==

Latest revision as of 14:06, 1 September 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Moises Romo M.D.

Overview

Neurofibromatosis type 1 is an autosomal syndrome caused by a mutation in gene NF1 of chromosome 17, wich leads to a defective neurofibromin 1 protein. This mutation constitutes a phenotype with very pathognomonic features that are not always present; among them are the presence of Lisch nodules, neurofibromas, scoliosis, cognitive disabilities, vision disorders, multiple café au lait spots and epilepsy.

Normal physiology

Pathogenesis and genetics

Associated conditions


Gross pathology

Microscopic pathology

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Rad E, Tee AR (April 2016). "Neurofibromatosis type 1: Fundamental insights into cell signalling and cancer". Semin. Cell Dev. Biol. 52: 39–46. doi:10.1016/j.semcdb.2016.02.007. PMID 26860753.
  2. ↑ Seminog OO, Goldacre MJ (January 2013). "Risk of benign tumours of nervous system, and of malignant neoplasms, in people with neurofibromatosis: population-based record-linkage study". Br. J. Cancer. 108 (1): 193–8. doi:10.1038/bjc.2012.535. PMC 3553528. PMID 23257896.
  3. ↑ Upadhyaya, Meena; Cooper, David N. (2012). doi:10.1007/978-3-642-32864-0. Missing or empty |title= (help)
  4. ↑ Peltonen S, Kallionpää RA, Peltonen J (July 2017). "Neurofibromatosis type 1 (NF1) gene: Beyond café au lait spots and dermal neurofibromas". Exp. Dermatol. 26 (7): 645–648. doi:10.1111/exd.13212. PMID 27622733.
  5. ↑ 5.0 5.1 Trovó-Marqui AB, Tajara EH (July 2006). "Neurofibromin: a general outlook". Clin. Genet. 70 (1): 1–13. doi:10.1111/j.1399-0004.2006.00639.x. PMID 16813595.
  6. ↑ 6.0 6.1 Boyd KP, Korf BR, Theos A (July 2009). "Neurofibromatosis type 1". J. Am. Acad. Dermatol. 61 (1): 1–14, quiz 15–6. doi:10.1016/j.jaad.2008.12.051. PMC 2716546. PMID 19539839.
  7. ↑ 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 Gutmann DH, Ferner RE, Listernick RH, Korf BR, Wolters PL, Johnson KJ (February 2017). "Neurofibromatosis type 1". Nat Rev Dis Primers. 3: 17004. doi:10.1038/nrdp.2017.4. PMID 28230061.
  8. ↑ Harrisingh, Marie C.; Lloyd, Alison C. (2014). "Ras/Raf/ERK signalling and NF1: Implications for Neurofibroma Formation". Cell Cycle. 3 (10): 1255–1258. doi:10.4161/cc.3.10.1182. ISSN 1538-4101.
  9. ↑ Wang, Yuan; Kim, Edward; Wang, Xiaojing; Novitch, Bennett G.; Yoshikawa, Kazuaki; Chang, Long-Sheng; Zhu, Yuan (2012). "ERK Inhibition Rescues Defects in Fate Specification of Nf1-Deficient Neural Progenitors and Brain Abnormalities". Cell. 150 (4): 816–830. doi:10.1016/j.cell.2012.06.034. ISSN 0092-8674.
  10. ↑ Dodd KM, Yang J, Shen MH, Sampson JR, Tee AR (April 2015). "mTORC1 drives HIF-1α and VEGF-A signalling via multiple mechanisms involving 4E-BP1, S6K1 and STAT3". Oncogene. 34 (17): 2239–50. doi:10.1038/onc.2014.164. PMC 4172452. PMID 24931163.
  11. ↑ Messiaen LM, Callens T, Mortier G, Beysen D, Vandenbroucke I, Van Roy N, Speleman F, Paepe AD (2000). "Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects". Hum. Mutat. 15 (6): 541–55. doi:10.1002/1098-1004(200006)15:6<541::AID-HUMU6>3.0.CO;2-N. PMID 10862084.
  12. ↑ DeClue JE, Cohen BD, Lowy DR (November 1991). "Identification and characterization of the neurofibromatosis type 1 protein product". Proc. Natl. Acad. Sci. U.S.A. 88 (22): 9914–8. doi:10.1073/pnas.88.22.9914. PMC 52837. PMID 1946460.
  13. ↑ Friedrich RE, Schmelzle R, Hartmann M, Fünsterer C, Mautner VF (January 2005). "Resection of small plexiform neurofibromas in neurofibromatosis type 1 children". World J Surg Oncol. 3 (1): 6. doi:10.1186/1477-7819-3-6. PMC 549083. PMID 15683544.
  14. ↑ "Neurofibromatosis type II - Wikipedia".
  15. ↑ 15.0 15.1 De Schepper S, Maertens O, Callens T, Naeyaert JM, Lambert J, Messiaen L (April 2008). "Somatic mutation analysis in NF1 café au lait spots reveals two NF1 hits in the melanocytes". J. Invest. Dermatol. 128 (4): 1050–3. doi:10.1038/sj.jid.5701095. PMID 17914445.
  16. ↑ 16.0 16.1 16.2 16.3 16.4 16.5 Cimino PJ, Gutmann DH (2018). "Neurofibromatosis type 1". Handb Clin Neurol. 148: 799–811. doi:10.1016/B978-0-444-64076-5.00051-X. PMID 29478615.
  17. ↑ 17.0 17.1 "Clinical and genetic patterns of neurofibromatosis 1 and 2. | British Journal of Ophthalmology".
  18. ↑ . doi:10.1016/j.jpeds.2006.10.048Get rights and content Objective Check |doi= value (help). Missing or empty |title= (help)
  19. ↑ Rodriguez FJ, Folpe AL, Giannini C, Perry A (March 2012). "Pathology of peripheral nerve sheath tumors: diagnostic overview and update on selected diagnostic problems". Acta Neuropathol. 123 (3): 295–319. doi:10.1007/s00401-012-0954-z. PMC 3629555. PMID 22327363.
  20. ↑ Lewis, Richard Alan; Gerson, L. Paul; Axelson, Kenneth A.; Riccardi, Vincent M.; Whitford, Randolph P. (1984). "von Recklinghausen Neurofibromatosis". Ophthalmology. 91 (8): 929–935. doi:10.1016/S0161-6420(84)34217-8. ISSN 0161-6420.
  21. ↑ Rosser, T. L.; Vezina, G.; Packer, R. J. (2005). "Cerebrovascular abnormalities in a population of children with neurofibromatosis type 1". Neurology. 64 (3): 553–555. doi:10.1212/01.WNL.0000150544.00016.69. ISSN 0028-3878.
  22. ↑ Bajenaru ML, Hernandez MR, Perry A, Zhu Y, Parada LF, Garbow JR, Gutmann DH (December 2003). "Optic nerve glioma in mice requires astrocyte Nf1 gene inactivation and Nf1 brain heterozygosity". Cancer Res. 63 (24): 8573–7. PMID 14695164.

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