Intermediate Charcot-Marie-Tooth disease due to a novel Trp101Stop myelin protein zero mutation associated with debilitating neuropathic pain.
We report an English kindred affected across 4 generations with a hereditary neuropathy associated with debilitating neuropathic pain as the main clinical feature. The principal finding on clinical examination was sensory loss, and there was variable motor dysfunction. Electrophysiological studies revealed mild features of demyelination with median conduction velocity in the intermediate range. There was an autosomal-dominant pattern of inheritance, and genetic testing revealed a novel heterozygous Trp101X mutation in exon 3 coding for a portion of the extracellular domain of myelin protein zero. This is predicted to lead to premature termination of translation. Myelin protein zero is a key structural component of compact myelin, and over 100 mutations in this protein have been reported, which can give rise to neuropathies with either axonal, demyelinating, or intermediate features encompassing a wide range of severity. Chronic pain is an increasingly recognised sequela of certain hereditary neuropathies and may be musculoskeletal or neuropathic in origin. In this kindred, the neuropathy was relatively mild in severity, however, neuropathic pain was an important and disabling outcome.
Wolfson Centre for Age-Related Diseases, King's College London, London, UK Medical Director's Office, Western Sussex Hospitals, Worthing, UK Department of Clinical Neurosciences, King's College, London, UK.
Juan D
JD
Ramirez
Phillip R J
PRJ
Barnes
Kerry R
KR
Mills
David L H
DLH
Bennett
D000293:Adolescent; D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D018993:Myelin P0 Protein / Q000235:genetics*; D009437:Neuralgia / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055815:Young Adult
D005819:Genetic Markers; C560547:MPZ protein, human; D018993:Myelin P0 Protein