Type 2E and Neurofilaments

[Guest guest]

,

Thanks for the introduction. I too really do not like anything on my

feet - and that's been since I was 7. Do you mean DAFOs for easy-gait?

Here is an report I wrote for CMT Today last year on neurofilaments and

2E. All my research at the time said it presented in one's 20's, but we

all know CMT genetics is rapidly evolving. ~ Gretchen

Neurofilaments

By Gretchen Glick

Neurofilaments are fine, long threads with major proteins stretching out

in a mesh pattern. They affect the nervous system tissue and are found

in axons. (nerves) Mutations in some of the neurofilament proteins have

been shown to cause one of the CMT type 2 subtypes, such as Type 2E.

2E was first found in a Russian family backgrounds and is dominantly

inherited. Onset is in the second or third decades ( in one's 20's or

30's) and has characteristics of distal sensory loss, leak weakness,

difficulty walking, reduced tendon reflexes, 100% pes cavus foot over

the age of 20 and either normal or slightly reduced EMG/NCV results.

Type 2E is also known to have a very slow progression rate.

A DNA blood test for diagnosis of CMT for 2E is able to locate the 2E

mutation to chromosome arm 8p21. Persons with this subtype can now also

undergo Pre-Implantation Genetic Diagnosis and thereby not pass CMT on

to their offspring. (PGID is a type of in vitro fertilization in which

the gene causing Type 2E is omitted) This has been successfully

completed with a number of CMT affected parents and their children do

not have CMT.

Neurofilaments are distinct to axons, but are found in other cell types

like keratin of the skin. Earlier this year, a team of researchers at

Columbia University examined CMT persons in order to observe the role of

mutated neurofilaments and observe exactly how the mutated

neurofilaments affect CMT.

Some researchers suggest that mutations in neurofilaments upset the

transport of nerve signals. Others suggest abnormal clusters of these

proteins cause nerve cell degeneration and death.

English researchers discovered that mutations of neurofilament proteins

block transport of mitochondria through the axon. Mitochondria contains

genetic material and many enzymes important for cell metabolism,

including those used in converting food to energy. These researchers

theorize that it is that the lack of mitochondria that starves axons of

energy leading to degeneration and death.

Neurofilaments are composed of three major subunits known as NF-L, NF-M

and NF-H ( meaning their axonal or nerve position). More recently,

research now realizes that neurofilaments also contain vital proteins

which are essential to a healthy, functioning nerve network.

Type 1F demylenating CMT has been found on Chromosome 8p21, like 2E, and

is also important to neurofilament light chain discoveries. While still

in research stages, arrestment may be soon due to further genetic

mapping and development of DNA testing. CMT 1F is characterized with

onset before age 13, delayed walking and motor skills, both arm and leg

weakness with atrophy, tremor and absent or reduced reflexes.

Copyright 2003 TF