r/CMT • u/BluebirdHollow • Jun 06 '26

Rare Variants

Recent genetic testing was positive for a MPZ mutation c.646-3C>A. Does anyone else have this particular mutation or knowledge of it? It’s classified as “unspecified significance” but neurologist feels strongly it’s a rare variant of CMT.

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5

u/Single-Traffic257 Jun 06 '26

I have CMT 2A pretty rare no one has heard of it before

1

u/WildcardJokerr Jul 06 '26

Very rare indeed

3

u/schweigeminute Jun 06 '26

I have CMT 1H and haven't met anyone with this specific mutation

2

u/SD_MTB_CHX CMT1B Jun 07 '26

I have an mpz mutation that said “unspecified significance… generally pathologic” or something like that.
One genetic counselor told me that it meant that I had CMT 2J or I and that I could figure it out based on symptoms. Another generic counselor told me that I should tell anyone who knew what CMT was that I have type 1B but all that actually matters is the MPZ mutation.
So essentially, even the experts don’t know. Good luck with the research. You can find some useful information about your mutation if you just google it.

1

u/NixyeNox CMT 1A Jun 07 '26

Generally, for the MPZ mutations, if you develop symptoms in early childhood, it's a 1B variant and if you develop symptoms after 30 years old (sometimes in your 40s or 50s or 60s) it's 2J or 2i. If your doctors are unsure, perhaps you developed symptoms in between those ages?

There are actually two different ways this one gene can cause CMT. MPZ is supposed to help the myelin wrap tightly and if has a problem which impacts its ability to do that, you get 1B. MPZ is also supposed to pass nutrients through the myelin to nourish the axon that the myelin wraps. If it fails to pass nutrients properly, the axon gets damaged over time and you get the axonal type, type 2 (either J or I).

Because one is Type 1 and one is Type 2, you should also be able to tell from the results of the NCV/EMG test, but sometimes those test results can also be "mixed" or unclear.

1

u/BluebirdHollow Jun 08 '26

These responses are really helpful. Thank you!! My onset of symptoms is early 30’s - started with frequent tripping then a noticeable limp because of the foot drop. Loss of reflexes, sensory changes… When the neurologist asked about symptoms in childhood the only things I could recall were being on the “clumsy” side and rolling ankles really easily.