T118M PMP22 mutation causes partial loss of function and HNPP-like neuropathy.
OBJECTIVE
To determine the clinical consequences of the PMP22 point mutation, T118M, which has been previously considered to either cause an autosomal recessive form of Charcot-Marie-Tooth (CMT) disease or be a benign polymorphism.


METHODS
We analyzed patients from five separate kindreds and characterized their peripheral nerve function by clinical and electrophysiological methods.


RESULTS
All heterozygous patients had clinical and/or electrophysiological features of a neuropathy similar to hereditary neuropathy with liability to pressure palsies (HNPPs). The homozygous patient had a severe axonal neuropathy without features of demyelination.


CONCLUSIONS
These findings suggest that T118M PMP22 retains some normal PMP22 activity, allowing the formation of compact myelin and normal nerve conduction velocities in the homozygous state. Taken together, these findings suggest that T118M is a pathogenic mutation causing a dominantly inherited form of CMT by a partial loss of PMP22 function.
Shy
Michael E
ME
Department of Neurology and Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA. m.shy@wayne.edu
Scavina
Mena T
MT
Clark
Alisa
A
Krajewski
Karen M
KM
Li
Jun
J
Kamholz
John
J
Kolodny
Edwin
E
Szigeti
Kinga
K
Fischer
Richard A
RA
Saifi
Gulam Mustafa
GM
Scherer
Steven S
SS
Lupski
James R
JR
D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology*; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009185:Myelin Proteins / Q000235:genetics*; D009431:Neural Conduction / Q000502:physiology; D010525:Peripheral Nerves / Q000503:physiopathology; D010641:Phenotype; D013912:Threonine / Q000235:genetics*
D009185:Myelin Proteins; C073687:PMP22 protein, human; D013912:Threonine; D008715:Methionine