X linked demylinating research - Seattle/U.S.A.

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1: Neuromuscul Disord 2002 Oct;12(7-8):643

Charcot-Marie-Tooth neuropathy: clinical phenotypes of four novel

mutations in the MPZ and Cx 32 genes.

Street V, Meekins G, Lipe H, Seltzer W, G, Kraft G, Bird T.

Bloedel Hearing Center, University of Washington, 98195, Seattle, WA,

USA

Charcot-Marie-Tooth Hereditary Neuropathy is a heterogeneous syndrome

associated with mutations in several different genes including

peripheral myelin protein 22, myelin P0, connexin 32, and early growth

response 2. There is considerable variability in the

phenotypic expression of this syndrome and the relationship of this

variability to mutation genotypes requires extensive analysis. Here we

describe the phenotypes

and genotypes of four new mutations underlying the Charcot-Marie-Tooth

syndrome and document segregation with disease. Four families with

Charcot-Marie-Tooth were ascertained, examined, and evaluated

electrophysiologically. Each family had peripheral blood DNA screened

for mutations in myelin protein 22, myelin P0, and

connexin 32. Two families were found with new mutations in the myelin P0

gene: S140T in the extracellular domain and K236del in the cytoplasmic

domain. All families showed segregation of the mutations with the

Charcot-Marie-Tooth phenotype as did a new family with the rare G163R

mutation in the membrane domain. A 49-year-old man with

the S140T electrophysiological testing. A family with a novel S49P

mutation in the connexin 32 gene had a neuropathy with very slow nerve

conduction. These new

mutations in the myelin P0 and connexin 32 genes help to clarify the

pathophysiology of the clinical Charcot-Marie-Tooth syndrome. The S140T

mutation in myelin P0 can be associated with conduction block and

Charcot-Marie-Tooth should be part of the differential diagnosis of that

phenomenon. Mutations in the cytoplasmic domain of myelin P0 can cause

clinical neuropathy. The S49P mutation in the connexin 32

gene can produce aspects of a demyelinating type of X-linked hereditary

neuropathy.