Premium
Charcot–Marie–Tooth disease and related neuropathies: Molecular basis for distinction and diagnosis
Author(s) -
Pareyson Davide
Publication year - 1999
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/(sici)1097-4598(199911)22:11<1498::aid-mus4>3.0.co;2-9
Subject(s) - peripheral myelin protein 22 , myelin , disease , genetics , phenotype , gene , biology , hereditary motor and sensory neuropathy , molecular genetics , degenerative disease , loss function , mutation , medicine , pathology , neuroscience , central nervous system
Great advances have been made in understanding the molecular basis of Charcot‐Marie‐Tooth disease (CMT) and related neuropathies, namely Dejerine‐Sottas disease (DSD), hereditary neuropathy with liability to pressure palsies (HNPP) and congenital hypomyelination (CH). The number of newly uncovered mutations and identified genetic loci is rapidly increasing, and, as a consequence, the classification of these disorders is becoming more complicated. Molecular genetics, animal models, and transfected cell studies are shedding light on function and dysfunction of proteins involved in hereditary myelinopathies—peripheral myelin protein 22 (PMP22), myelin protein zero (PO), connexin 32 (Cx32), and early growth response 2 (EGR2). Gene dosage effect, loss of function, gain of toxic function, and dominant negative effect are possible mechanisms whereby different gene mutations may exert their detrimental action on peripheral nerves. A tentative rational approach to clinical and molecular diagnosis based on genotype–phenotype correlation analysis is described. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 1498–1509, 1999