Editing Neurofibromatosis (section)

==Pathophysiology==
The pathophysiology is varied, and each NF type has a different one:

* '''Neurofibromatosis type I''' is the most common of the three types and is caused by genetic changes in the NF1 gene located on chromosome 17 (17q11.2). This gene encodes a cytoplasmic protein known the neurofibromin, which functions as a [[tumor suppressor]] and therefore serves as a signal regulator of [[cell proliferation]] and differentiation.<ref>{{Cite journal |last1=Wallace |first1=Margaret R. |last2=Marchuk |first2=Douglas A. |last3=Andersen |first3=Lone B |last4=Letcher |first4=Roxanne |last5=Odeh |first5=Hana M. |last6=Saulino |first6=Ann M. |last7=Fountain |first7=Jane W. |last8=Brereton |first8=Anne |last9=Nicholson |first9=Jane |last10=Mitchell |first10=Anna L. |last11=Brownstein |first11=Bernard H. |last12=Collins |first12=Francis S. |date=1990-07-13 |title=Type 1 Neurofibromatosis Gene: Identification of a Large Transcript Disrupted in Three NF1 Patients |url=http://dx.doi.org/10.1126/science.2134734 |journal=Science |volume=249 |issue=4965 |pages=181–186 |doi=10.1126/science.2134734 |pmid=2134734 |bibcode=1990Sci...249..181W |issn=0036-8075}}</ref><ref>{{Cite web |title=Orphanet: Neurofibromatosis type 1 |url=http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=636 |url-status=live |archive-url=https://web.archive.org/web/20151006061921/http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=636 |archive-date=6 October 2015 |access-date=2015-10-13 |website=www.orpha.net}}</ref> A dysfunction or lack of neurofibromin can affect regulation, and cause uncontrolled cell proliferation, leading to the tumors (neurofibromas) that characterize NF1. The neurofibromas caused by NF consist of Schwann cells, fibroblasts, perineuronal cells, mast cells and axons embedded in an extracellular matrix.<ref name=":2">{{Cite journal |vauthors=Ferner RE |date=February 2007 |title=Neurofibromatosis 1 |journal=European Journal of Human Genetics |volume=15 |issue=2 |pages=131–138 |doi=10.1038/sj.ejhg.5201676 |pmid=16957683 |doi-access=free}}</ref><ref>{{Cite journal |vauthors=Boyd KP, Korf BR, Theos A |date=July 2009 |title=Neurofibromatosis type 1 |journal=Journal of the American Academy of Dermatology |volume=61 |issue=1 |pages=1–14 |doi=10.1016/j.jaad.2008.12.051 |pmc=2716546 |pmid=19539839}}</ref> Another function of neurofibromin is to bind to microtubules that play a role in the release of [[adenylyl cyclase]] and its activity.<ref name=":2" /> Adenylyl cyclase plays an essential role in cognition.<ref name=":2" /> Neurofibromin's role in the activity of adenylyl cyclase explains why patients with NF experience cognitive impairment.<ref name=":2" />

* '''Neurofibromatosis type II''' is caused by a mutation on chromosome 22 (22q12).<ref name=":3">{{Cite journal |vauthors=Lin AL, Gutmann DH |date=November 2013 |title=Advances in the treatment of neurofibromatosis-associated tumours |journal=Nature Reviews. Clinical Oncology |volume=10 |issue=11 |pages=616–624 |doi=10.1038/nrclinonc.2013.144 |pmid=23939548 |s2cid=21986493}}</ref> The mutation falls on the NF2 tumor suppressor gene.<ref name=":3" /> The gene normally encodes a cytoplasmic protein known as [[Merlin (protein)|merlin]]. The normal function of merlin is to regulate the activity of multiple growth factors, the mutated copy of the gene leads to merlin's loss of function.<ref name=":3" /> The loss of function leads to increased activity of growth factors normally regulated by merlin, leading to the formation of the tumors associated with NF2.<ref name=":3" />

* '''Schwannomatosis''' is caused by a mutation on the [[SMARCB1]] gene.<ref name=":42">{{Cite journal |display-authors=6 |vauthors=Plotkin SR, Blakeley JO, Evans DG, Hanemann CO, Hulsebos TJ, Hunter-Schaedle K, Kalpana GV, Korf B, Messiaen L, Papi L, Ratner N, Sherman LS, Smith MJ, Stemmer-Rachamimov AO, Vitte J, Giovannini M |date=March 2013 |title=Update from the 2011 International Schwannomatosis Workshop: From genetics to diagnostic criteria |journal=American Journal of Medical Genetics. Part A |volume=161A |issue=3 |pages=405–416 |doi=10.1002/ajmg.a.35760 |pmc=4020435 |pmid=23401320}}</ref> This gene is located near the NF2 tumor suppressor gene leading to the thought that schwannomatosis and NF2 were the same condition. The two conditions show different mutations on two different genes. The normal function of the SMARCB1 gene is to encode a protein called SMARCB1 that is part of a larger protein complex whose function is not completely understood.<ref name=":42" /> The complex including SMARCB1 plays a role in tumor suppression.<ref name=":42" /> The mutation of the SMARCB1 gene causes a loss of function in the complex leading to the formation of tumors indicative of schwannomatosis.<ref name=":42" />