View source for Charcot-Marie-Tooth Syndrome

This is a large group of genetic [[Neuropatie a nervosvalová onemocnění/PGS|neuropathies]]. Sometimes referred to as '''CMT'''. Degenerative changes affect both the '''motor''' and '''sensory''' components. The changes are most pronounced on the lower limb, especially on the feet. It is one of the most common '''hereditary neuropathies'''.

== CMT classification ==
[[File:Onion bulb formation HMSN.jpg|thumb|"Onion bulb formations" in nerve biopsy ]]
CMT is divided into five basic groups:
* CMT1 - is [[autosomal dominantly]] inherited. It is further divided into 6 subtypes (CMT1A to CMT1F)
* CMT2 - is [[autosomal dominantly]] inherited. It contains 11 subtypes, designated CMT2A – L, while subtype B is then further subdivided (B, B1, B2).
* CMT3 - is [[autosomal recessively]] inherited. Extremely rare form. It has no further division.
* CMT4 - is [[autosomal recessively]] inherited. Extremely rare form. Contains 8 types of CMT4A-J, with diversified group B (B1, B2)
* CMTX - has [[gonosomal inheritance]]. There are 5 subtypes marked with numbers, ie CMTX1–5

== Genetic nature of CMT ==
[[File:Charcot-marie-tooth foot.jpg|thumb|Manifestation of CMT syndrome]]
Recent studies list 39 different [[genes]] whose [[mutations]] cause some form of CMT.

Probably the most common mutation that causes the first type of CMT, '''CMT1A''' (and also '''CMT1E''') is a mutation in the [http://omim.org/entry/601097 '''PMP22'''] gene, the product is a [[protein]] called '''peripheral myelin protein 22'''. It is a transmembrane protein contained mainly in the membrane of [[Neuroglie|Schwann cells]], it passes through the membrane 4 times and is incorporated into the structure of [[myelin]]. Dozens of gene sites are known in which a point mutation causes CMT.

A less common mutation is a mutation in the gene for the so-called [http://omim.org/entry/159440 '''MPZ'''] protein, ie '''myelin protein zero'''. It is one of the most important proteins in the '''formation and maintenance''' of the myelin sheath. It is a transmembrane protein, also part of the Schwann cell membrane, which passes through the membrane only once. It belongs to the [[immunoglobulin]] family, has [[extracellular]], transmembrane and intracellular domains. It forms a homotetramer and its function is that the two homotetramers combine when the individual leaves of the Schwann cell membrane fold together due to their extracellular domains. This keeps the structure of the myelin sheath firm. Mutations in the MPZ gene cause CMT1B and CMT2J.

* CMT1C is caused by a mutation in the [http://omim.org/entry/603795 '''LITAF'''] gene, a ''lipopolysaccharide-induced tumor necrosis factor-alpha factor''. According to the latest research, it is associated with obesity and insulin resistance.
* CMT1D and CMT4E are caused by a mutation in the [http://omim.org/entry/129010 '''EGR2'''] gene, ''early growth response protein 2''.
* CMT1F and CMT2E cause mutations in the [http://omim.org/entry/162280 '''NEFL'''] gene, a ''neurofilament light polypeptide''.
* The mutation in the [[mitofusin 2]] gene is responsible for CMT2A.
* CMT3, termed '''Dejerine-Sottas syndrome''', is associated with the PMP22, MPZ, EGR2 and PRX (''periaxin'') genes.

Other types of CMT are caused by mutations in many other genes (if identified). Probably the latest discovery is the clarification of the cause of CMTX5, which is the gene for [http://omim.org/entry/311850 '''PRPS1'''], ie ''phosphoribosyl pyrophosphate synthetase 1''.

<noinclude>

== Links ==
=== External links ===
* '''Databáze OMIM'''
** [http://omim.org/entry/601097 gen PMP22]
** [http://omim.org/entry/159440 gen MPZ]
** [http://omim.org/entry/603795 gen LITAF]
** [http://omim.org/entry/129010 gen EGR2]
** [http://omim.org/entry/162280 gen NEFL]
** [http://omim.org/entry/608506 gen MFN1]
** [http://omim.org/entry/608507 gen MFN2]
** [http://omim.org/entry/311850 gen PRPS1]


* Other:
** [https://en.wikipedia.org/wiki/PMP22 Wikipedia – PMP22 ]
** [https://en.wikipedia.org/wiki/Charcot%E2%80%93Marie%E2%80%93Tooth_disease Wikipedia – Charcot–Marie–Tooth disease]
** [https://en.wikipedia.org/wiki/LITAF Wikipedia – LITAF]
** [https://en.wikipedia.org/wiki/EGR2 Wikipedia – EGR2]
** [https://en.wikipedia.org/wiki/NEFLW Wikipedia – NEFLW]
** [https://en.wikipedia.org/wiki/Dejerine-Sottas_disease Dejerine-Sottas disease]
=== References ===
*[[ws:Charcotův-Marieův-Toothův syndrom]]
* {{Cite
| type = web
| url = http://structbio.vanderbilt.edu/sanders/Research_Julia_Ver_1/Research.html
| surname1 = Sanders
| name1 = Charles
| others = yes
| source_name = Peripheral Myelin Protein 22
| publisher = Sander's lab
| cited = 2011-04-15
}}
* {{Cite
| type = web
| url = http://www.nejm.org/action/cookieAbsent
| surname1 =  Triggs
| name1 = William J.
| others = yes
| source_name = A 57-Year-Old Woman with Numbness and Weakness of the Feet and Legs
| publisher = NEJM
| cited = 2011-04-15
}}
* {{Cite
| type = web
| url = https://www.ncbi.nlm.nih.gov/pubmed/17701900
| surname1 =  Hee-Jin  
| name1 = Kim
| others = yes
| source_name = Mutations in PRPS1
| cited = 2011-04-15
}}
* [https://www.ncbi.nlm.nih.gov/pubmed?term=LITAF LITAF]
</noinclude>

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[[Category:Pathology]]
[[Category:Neurology]]
[[Category:Genetics]]