Genetic epidemiology of Charcot-Marie-Tooth in the general population.
OBJECTIVE
the frequency of different Charcot-Marie-Tooth (CMT) genotypes has been estimated in clinic populations, but prevalence data from the general population are lacking.


METHODS
our population-based genetic epidemiological survey included persons with CMT residing in eastern Akershus County, Norway. The participants were interviewed and examined by one geneticist/neurologist and classified clinically, neurophysiologically and genetically.


RESULTS
two hundred and forty-five persons from 116 families had CMT. This corresponds to 1 per 1214 persons (95% CI 1062-1366) have CMT in the general population. CMT1 (motor conduction velocity (MCV) <38 m/s), CMT2 (MCV >38 m/s) and CMT intermediate (MCV 25-45 m/s) were found in 48.2%, 49.4% and 2.4% of the families. A total of 27.2% of the families and 28.6% of the affected had a mutation in the investigated CMT genes. The prevalence of the peripheral myelin protein 22 (PMP22) duplication and point mutation in the connexin32 (Cx32), myelin protein zero (MPZ) and mitofusin2 (MFN2) genes was found in 13.6%, 6.2%, 1.2%, 6.2% of the families, and in 19.6%, 4.8%, 1.1%, 3.2% of the affected, respectively. None of the families had point mutations in the early growth response 2 (EGR2), PMP22 or small integral membrane protein of lysosome/late endosome (SIMPLE) genes.


CONCLUSIONS
CMT is the most common inherited neuropathy. At present, 43 CMT genes are known, and an examination of all known genes would probably only identify mutations in approximately 50% of those with CMT. Thus, it is probable that at least 30-50 CMT genes are yet to be identified.
Braathen
G J
GJ
Faculty Division Akershus University Hospital, University of Oslo, Norway. g.j.braathen@medisin.uio.no
Sand
J C
JC
Lobato
A
A
Høyer
H
H
Russell
M B
MB
D002607:Charcot-Marie-Tooth Disease / Q000453:epidemiology* / Q000235:genetics*; D017630:Connexins / Q000235:genetics; D005260:Female; D020558:GTP Phosphohydrolases; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics; D009154:Mutation; D018993:Myelin P0 Protein / Q000235:genetics; D009185:Myelin Proteins / Q000235:genetics; D009664:Norway / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D015995:Prevalence; D044465:White People / Q000235:genetics; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D020558:GTP Phosphohydrolases; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018993:Myelin P0 Protein; D009185:Myelin Proteins; D000097002:Gap Junction beta-1 Protein; C073687:PMP22 protein, human; C470018:MFN2 protein, human