A start codon CMT1X mutation associated with transient encephalomyelitis causes complete loss of Cx32

Neurogenetics
Irene SargiannidouKleopas A Kleopa

Abstract

X-linked Charcot-Marie-Tooth disease (CMTX1) results from numerous mutations in the GJB1 gene encoding the gap junction protein connexin32 (Cx32) and is one of the commonest forms of inherited neuropathy. Owing to the expression of Cx32 not only in Schwann cells but also in oligodendrocytes, a subset of CMT1X patients develops central nervous system (CNS) clinical manifestations in addition to peripheral neuropathy. While most GJB1 mutations appear to cause peripheral neuropathy through loss of Cx32 function, the cellular mechanisms underlying the CNS manifestations remain controversial. A novel start codon GJB1 mutation (p.Met1Ile) has been found in a CMT1X patient presenting with recurrent episodes of transient encephalomyelitis without apparent signs of peripheral neuropathy. In order to clarify the functional consequences of this mutation, we examined the cellular expression of two different constructs cloned from genomic DNA including the mutated start codon. None of the cloned constructs resulted in detectable expression of Cx32 by immunocytochemistry or immunoblot, although mRNA was produced at normal levels. Furthermore, co-expression with the other major oligodendrocyte connexin, Cx47, had no negative effect on GJ form...Continue Reading

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Citations

Oct 17, 2018·Glia·Christos P PapaneophytouKleopas A Kleopa
Sep 10, 2018·Journal of Neurology, Neurosurgery, and Psychiatry·Georgios KoutsisGeorgia Karadima
Jun 25, 2019·Channels·Christos PapaneophytouKleopas A Kleopa
Mar 11, 2020·JIMD Reports·Willemijn F E KuperPeter M van Hasselt
May 5, 2017·Chinese Medical Journal·Yuan-Yuan LuYun Yuan
Jun 6, 2017·Journal of Neuroscience Research·Andrew S Lapato, Seema K Tiwari-Woodruff
Jan 6, 2021·Biomolecules·Marc MesnilDenis Sarrouilhe
Dec 31, 2020·Brain Sciences·Federica BosoGian Maria Fabrizi

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