*Se è presente compressione focale superimposta o intrappolamento (la compressione può avvenire in assenza di intrappolamento).
CIDP—polineuropatia demielinizzante infiammatoria cronica (chronic inflammatory demyelinating polyneuropathy); CMT—Charcot-Marie-Tooth; HNPP—neuropatia ereditaria con predisposizione alla paralisi da compressione (hereditary neuropathy with liability to pressure palsies); m/sec = metri al secondo
Trattamento del dolore
· Uno studio che ha esaminato 636 individui con CMT ha indicato che 440 (69%) degli interpellati avevano significativi problemi di dolore. Il dolore lombare diffuso, poco localizzabile era comune (70%), come il bruciore ai piedi (44%). L’intensità del dolore riferita dai pazienti con CMT in questo studio era comparabile all’intensità riferita da pazienti con altre condizioni neuropatiche (nevralgia post-herpetica, neuropatia diabetica dolorosa e danno del nervo periferico) che hanno partecipato ad uno studio simile mentre frequentavano un centro universitario di gestione del dolore.
Sfortunatamente, nessuno studio ha esaminato specificatamente il
trattamento del dolore nella CMT. Un gruppo di farmaci potenzialmente
neurotossici dovrebbero senz’altro essere evitati dai pazienti con CMT.
Questo elenco include molti agenti chemioterapeutici, in particolare
vincristina, paclitaxel e cisplatin. Un elenco completo dei farmaci che
possono potenziare o inasprire i sintomi neuropatici nella CMT lo trovate
Indichiamo sotto due articoli scientifici che aprono un nuovo spiraglio su di un possibile trattamento per le neuropatie.
SCOPERTA PROTEINA CHE RIPARA IL TESSUTO NERVOSO
Una ricerca ad ampio raggio, che ha visto la collaborazione
degli scienziati del Peninsula Medical School, dell'University College di Londra
e del Cancer Research nel Regno Unito e del San Raffaele di Milano, ha
individuato una proteina che gioca un ruolo fondamentale nella
rigenerazione dei danni nel sistema nervoso periferico. Lo studio compare
su Journal of Cell Biology.
Turning back the clock for Schwann cells
Myelin-making Schwann cells have an
ability every aging
Wrapped around neurons in the peripheral nervous system, Schwann cells can “dedifferentiate” into a state in which they can’t manufacture myelin. Reverting to an immature type of cell speeds healing of injured nerves. Researchers knew that the protein Krox-20 pushes immature Schwann cells to specialize and form myelin, but they didn’t know what prompts the reversal. One suspect was a protein called c-Jun, which youthful Schwann cells make but Krox-20 blocks.
Parkinson et al. cultured neurons with Schwann cells whose c-Jun gene they could activate. Turning on the gene curbed myelination, suggesting that c-Jun prevents young Schwann cells from growing up. c-Jun also prodded mature Schwann cells to become youthful again, the researchers discovered. Schwann cells that are separated from neurons normally dedifferentiate, but the team found that the cells remained specialized if c-Jun was missing. They suspect that c-Jun works in part by activating Sox-2, as this protein also inhibits myelination.
The researchers now want to investigate whether c-Jun is involved in illnesses where myelin dwindles, such as Charcot-Marie Tooth disease and Guillain-Barre syndrome. The results might also provide clues about multiple sclerosis, in which immune attacks destroy myelin in the central nervous system. Unlike Schwann cells, oligodendrocytes, the myelin makers in the central nervous system, can’t revert to an immature state. Whether c-Jun affects oligodendrocyte differentiation isn’t known.
Parkinson, D.B., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200803013.
USO STUDIO COMPLETO SU TUTTO QUANTO E’ STATO SCOPERT O SINO AD OGGI SU LE POSSIBILITA’ DIAGNOSTICHE E TERAPEUTICHE DELLA CMT
N.B. L’articolo è in fase di traduzione, e sarà pubblicato in italiano tra poco tempo.
Gregory T. Carter, MD
Michael D. Weiss, MD
Jay J. Han, MD
Phillip F. Chance, MD
John D. England, MD
Gregory T. Carter, MD
Department of Rehabilitation Medicine, Box 356490, University of Washington, 1959 N.E. Pacific Avenue, Seattle, WA 98195, USA. E-mail: email@example.com
Current Treatment Options in Neurology 2008, 10:94–102 Current Medicine Group LLC ISSN 1092-8480
Copyright © 2008 by Current Medicine Group LLC
The family of hereditary peripheral neuropathies that makes up Charcot-Marie-Tooth
disease (CMT) comprises some of the most common neuromuscular disorders. Over
the past decade, understanding of the molecular basis of CMT has increased enormously.
In addition, the neurophysiologic deficits and clinical problems associated
with CMT are more clearly delineated, and the precise genetic cause of many types
of CMT has now been determined. Advances in molecular biology and genetic manipulation
techniques have allowed the development of animal models of some of
these CMT types, allowing more productive scientific exploration of possible treatments.
Recent treatment advances that have been effective in animal models include
oral supplementation with curcumin and vitamin C (ascorbic acid), and the use of
onapristone, a progesterone antagonist. Human trials with vitamin C are currently
in progress. While ongoing molecular genetic research continues to identify more
of the mutant genes and proteins that cause the various disease subtypes, clinical
research should continue to focus on developing pharmaceutical and rehabilitative
therapies to ameliorate nerve degeneration and ultimately improve function for patients
with CMT. These patients optimally should be managed in a comprehensive,
multidisciplinary setting involving neurologists, physiatrists, orthopedic surgeons,
physical and occupational therapists, and orthotists. Treatment should be aimed at
maximizing independence and quality of life.
Over the past decade, understanding of the molecular
basis of Charcot-Marie-Tooth disease (CMT) has
increased enormously, and the neurophysiologic deficits
and clinical problems associated with CMT have
been more clearly delineated. This article discusses the
management of CMT, including novel and promising
therapeutic interventions that potentially could be used
as part of a treatment regimen. These interventions may
involve attempts to slow down or stop neurodegenerative
processes through nerve growth factors, limiting
oxidative stress by using antioxidants, or normalizing
gene expression through genetic manipulation. Other
potential therapeutic target areas include the progesterone
receptor on myelin-forming Schwann cells, the
immune system via modulation of nerve inflammation,
and enhanced glutathione transferase activity. While
ongoing molecular genetic research continues to identify
more of the mutant genes and proteins that cause the
various disease subtypes, clinical research should continue
to focus on developing pharmaceutical and rehabilitative
therapies to ameliorate nerve degeneration and
ultimately improve function for people with CMT.
GENOTYPES AND PHENOTYPES
Table 1 summarizes the genetic basis of the major forms
of CMT and related neuropathies. The disorders comprising
CMT1 are the most common types [1, Class
Charcot-Marie-Tooth Disease Carter et al. 95
Table 1. Summary of the genetic basis for Charcot-Marie-Tooth disease
Type Location Gene Inheritance Gene abnormality
CMT1A 17p11.2-12 PMP22 AD Duplication/point mutation
CMT1B 1q22-23 MPZ AD Point mutation
CMT1C 16p12-p13 SIMPLE AD Point mutation
CMT1D 10q21-q22 EGR2 AD/AR Point mutation
CMT2A 1p35-36 MFN2 AD Point mutation
CMT2B 3q13-q22 RAB7A AD Point mutation
CMT2C 12q23-q24 Unknown AD Unknown
CMT2D 7p14 GARS AD Point mutation
CMT2E 8p21 NEFL AD Point mutation
DSDA 17p11.2-12 PMP22 AD Point mutation
DSDB 1q22-23 MPZ AD Point mutation
DSDC 10q21-q22 EGR2 AD Point mutation
DSDD 19q13 PRX AR Point mutation
CMT4A 8q13-q21 GDAP1 AR Point mutation
CMT4B1 11q22 MTMR2 AR Point mutation
CMT4B2 11p15 SBF2 AR Point mutation
CMT4D 8q24 NDRG1 AR Point mutation
CMT4F 19q13 PRX AR Point mutation
CMTX Xq13.1 Cx32 XD Point mutation
Hereditary neuropathy with liability to pressure palsies (HNPP)
HNPP 17p11.2 PMP22 AD Deletion/point mutation
AD—autosomal dominant; AR—autosomal recessive; Cx32—connexin32; EGR2—early growth response 2; GARS—glycyl-tRNA synthetase;
GDAP1—ganglioside-induced differentiation-associated protein 1; MFN2—mitochondrial protein mitofusion 2; MPZ—myelin protein zero;
MTMR2—myotubularin-related protein 2; NDRG1—N-myc downstream regulated gene 1; NEFL—neurofilament, light polypeptide 68kDa;
PMP22—peripheral myelin protein 22; PRX—periaxin; RAB7A—small GTP-ase late endosomal protein gene 7; SBF2—SET binding factor 2;
SIMPLE—small integral membrane protein of late endosome; XD—X-linked dominant.
II]. Of these, the most common subtype is CMT1A,
resulting from a duplication of chromosome segment
17p11.2, which contains the gene for peripheral myelin
protein-22 (PMP22) [1,2, Class II,III].
Most of the phenotypic, descriptive studies in CMT were
done before the advent of DNA testing. Previous studies
have shown that, overall, CMT is a slowly progressive
disorder characterized by diffuse muscle weakness and
prominent distal atrophy, predominantly involving the
intrinsic muscles of the feet and the muscles innervated
by the peroneal nerve [3, Class II]. Patients with CMT
generate 20% to 40% less force than unaffected controls
using quantitative isometric and isokinetic strength measures,
even though manual muscle test (MMT) scores
may be normal [4, Class II]. There is no significant sideto-
side difference in strength [5–8, Class II,III]. From a
functional standpoint, the sensory deficit is usually less
severe than the motor deficit [1, Class II].
CMT2 is often clinically less severe than CMT1 [1, Class
II]. Patients with CMT2 may have more lower-extremity
involvement, although clinically they are not easily distinguished
from patients with CMT1 [1, Class II]. Bienfait et
al. [9, Class II] performed genetic analysis of the presently
known CMT2 genes on 61 persons from 18 families of
people with clinically determined CMT2. Ninety percent
of the patients were able to walk, either independently or
with the use of orthotics and walking aids such as a walker
or cane. Weakness of proximal leg muscles was present in
13%. Asymmetric features were present in
or brisk knee reflexes were present in 36%. Extensor plan
96 Neuromuscular Disorders
Table 2. Electrodiagnostic characteristics of the hereditary and acquired motor and sensory neuropathies
Neuropathy Conduction velocity characteristics Axonal loss
dispersion Focal slowing
CMT1 Uniform slowing, usually
< 38 m/sec but may be faster
CMT2 Minimal slowing to normal
CMT X1 Heterogeneous slowing
(30–40 m/sec); temporal dispersion
HNPP Nonuniform, intermediate
slowing, distal > proximal
Dejerine-Sottas Uniform, severe slowing
(< 20 m/sec)
Diabetic neuropathy Nonuniform, mild slowing
CIDP Nonuniform, multifocal,
to severe slowing
*If superimposed focal compression or entrapment is present (compression can occur in the absence of entrapment).
CIDP—chronic inflammatory demyelinating polyneuropathy; CMT—Charcot-Marie-Tooth; HNPP—hereditary neuropathy with liability to
pressure palsies; m/sec—meters per second.
tar responses without associated spasticity occurred in 10
patients from eight families. Mutations were present in
only three genes (MFN2, BSCL2, and RAB7). No mutations
were found in the NEFL, HSPB1, HSPB8, GARS,
DNM2, and GDAP1 genes. This is one of the largest studies
in CMT2 patients and confirms that, as a group, the
clinical phenotype is fairly uniform.
Table 2 summarizes the electrodiagnostic characteristics
of these inherited neuropathies and compares them with
some common acquired neuropathies. Electrodiagnosis
can divide CMT into two basic types,primarily demyelinating
(with secondary axonal loss) and primarily axonal
[10,11•,12,13, Class II,III].
Treatment of pain
A study surveying 636 individuals with CMT indicated that 440 (69%)
of the respondents had significant pain problems [14, Class II]. Dull,
aching, low back pain was common (70%), as was burning pain in
the feet (44%). The intensity of pain reported by CMT patients in this
study was comparable to the intensity of pain reported by patients with
other neuropathic conditions (postherpetic neuralgia, painful diabetic
neuropathy, and peripheral nerve injury), who participated in a similar
study while attending a university-based tertiary pain clinic.
Unfortunately, no studies have specifically examined the treatment of pain
in CMT. A number of potentially neurotoxic drugs should definitely be
avoided by patients with CMT. This list includes many chemotherapeutic
agents, most notably vincristine, paclitaxel, and cisplatin. A complete
list of drugs that may potentiate or exacerbate neuropathic symptoms in
CMT is maintained at http://www.hnf-cure.org/html/cmtrx.php.
Treatment of weakness and fatigue
Skeletal muscle weakness is the underlying cause of most clinical
problems in CMT. Several well-controlled, Class II studies have looked
at the effect of exercise as a means to gain strength in CMT and other
neuromuscular disorders [5,15–19, Class II,III]. In slowly progressive
neuromuscular disorders, including CMT, a 12-week exercise program
Charcot-Marie-Tooth Disease Carter et al. 97
using moderate resistance (30% of maximum isometric force) resulted
in strength gains ranging from 4% to 20% without any notable deleterious
effects [17, Class III]. In the same population, however, a 12-week
program using high resistance (training at the maximum weight the individual
could lift 12 times) showed no greater benefit than the moderateresistance
program, and some of the participants showed evidence of
overwork weakness [18, Class III]. The risk of muscle damage and
dysfunction secondary to exhaustive exercise may be significant, and
neuropathy patients should be advised not to overexercise [5, Class III].
In a comparative study, CMT patients appeared to benefit significantly
from a strengthening program, whereas patients in the same study with
myotonic muscular dystrophy showed neither beneficial nor detrimental
effects [5, Class II].
Fatigue is commonly reported by patients with CMT and may be at least
partly responsible for most clinical problems, ranging from pain to foot
drop [20•,21,22•,23–25, Class II–III]. A recent case series of four patients
showed promising relief of fatigue following modafinil treatment
[22•, Class III].
Orthotics and other equipment
Many patients with CMT require some form of bracing or orthotics for
their lower extremities, although no evidence better than Class III supports
this use [23, Class III]. Patients with CMT generally are not well served by
prefabricated orthotics. A custom-fitted device will provide more comfort
and better wearing compliance, and will reduce the risk of skin breakdown.
Other types of equipment that can substantially improve quality of life
include hand-held showers, bathtub benches, grab bars, raised toilet
seats, hospital beds, commode chairs, and aids to help with activities of
daily living, such as sock aids and grabbers. Again, evidence supporting
their use is based primarily on case series or expert consensus (Class III).
Wheeled walkers or quad (four-point) canes may also help, depending
on the pattern of weakness. Patients with severe CMT may require a
wheelchair [17,26, Class III].
Treatment for less common problems: breathing, hearing, swallowing
Electrodiagnosis and pathologic studies of the phrenic nerve confirm
that the phrenic nerve is involved in CMT [12,13, Class II]. Phrenic
nerve latencies are abnormally prolonged in most patients with CMT1
. Although phrenic nerve latencies are markedly prolonged in CMT,
they are not useful in predicting respiratory dysfunction. Rare patients
who develop respiratory failure can benefit from intermittent positive
pressure ventilation (IPPV) by mouth, avoiding tracheostomy and maintaining
a reasonable quality of life [27, Class III].
Other problems less often encountered in CMT include dysphagia with
vocal cord paralysis and sensorineural hearing loss [12, Class III]. A
recent study in CMT1A patients with normal peripheral hearing documented
subtle auditory processing problems [28,29, Class II]. There may
also be specific cranial nerve abnormalities, including papillary changes.
These subtle problems in CMT are postulated to be due to a specific
subset of genotypes involving the PMP22, MPZ, and EGR2 genes,
among others [30, Class II].
98 Neuromuscular Disorders
Nerve growth factors
Neurotrophic growth factors are naturally occurring polypeptides that
enhance nerve-cell survival in a multitude of animal models of neurodegeneration.
Various neurotrophic growth factors have been used, including
ciliary neurotrophic factor (CNTF), brain-derived neurotrophic
factor (BDNF), glial cell line–derived neurotrophic factor (GDNF), and
recombinant human insulin-like growth factor I (myotrophin) [31, Class
II]. Extensive study of these growth factors in the treatment of the motor
neuron disease amyotrophic lateral sclerosis (ALS) has not been successful.
A pilot trial of recombinant human neurotrophin-3 (NT-3), a growth
factor being developed by Regeneron
Pharmaceuticals, Inc. (
NY), yielded statistically significant improvements in nerve regeneration
and sensory function in four patients with CMT1A [32, Class II]. This
finding needs further study before any conclusions can be drawn.
Some evidence is emerging that CMT1A patients may have altered levels
of insulin, insulin-like growth factors (IGFs), and their binding proteins
(IGFBPs) [31, Class II]. Levels of both IGF-I and IGFBP-2 appear to be
increased, while serum levels of IGFBP-1 are decreased. Serum IGFs are
altered in animal models of diabetic neuropathy, in which serum insulin
levels are significantly decreased. In humans, these perturbations are probably
disease-specific and due to metabolic and endocrine derangements.
It is apparent that the DNA in forms of CMT due to a duplication in the
PMP22 gene does not regulate production of nerve growth factors [33,
Class III]. Thus, many gaps remain in our knowledge about identified gene
mutations in CMT, interactions between different genes, and the subsequent
clinical presentation of phenotype. It is unclear how this knowledge
will affect the development of potential treatments for CMT.
A number of other neurotrophic compounds show promise, including
synthetic compounds that mimic the activity of neurotrophins or stimulate
their biosynthesis via DNA alteration. New classes of small-molecule neurotrophic
factors called neuroimmunophilin ligands, such as FK-506, have the
advantage of oral administration; all other compounds in this class must be
injected. Emerging technology using viral vectors, such as an adeno-associated
viral (AAV) vector expressing IGF-1, may be a more efficient way of
delivering the neurotrophic factor to degenerating nerve cells.
Although not yet well studied in humans, the immune system has been implicated
as a possible therapeutic target in several murine models of CMT.
Mice heterozygously deficient in the peripheral myelin adhesion molecule
P0 (P0+/-mice) have both peripheral nerve demyelination and elevated
numbers of CD8-positive T lymphocytes and F4/80-positive macrophages.
These immune cells increase in number with age and progression of the
demyelination, suggesting that they may play a role in myelin damage.
These myelin mutant mice have been cross-bred with mice deficient in the
recombination activating gene 1 (RAG-1); these mice lack mature T and B
lymphocytes [34, Class II]. The immunodeficient myelin mutants showed
less-severe myelin degeneration. The beneficial effect of lymphocyte
deficiency was reversible; demyelination worsened in immunodeficient
myelin mutants when reconstituted with bone marrow from wild-type
mice. Ultrastructural analysis revealed macrophages in close apposition to
myelin and demyelinated axons. Thus, it appears that T lymphocytes and
macrophages may be involved in the pathogenesis of CMT and represent
Charcot-Marie-Tooth Disease Carter et al. 99
potential targets for pharmacologic manipulation. These studies in animal
models are encouraging and provide impetus for further work in humans,
but little work has yet been done.
A recent report described patients with genetically confirmed CMT and
another separate mutation, who developed severe, sudden deterioration
[33, Class III]. There was sufficient clinical, electrophysiologic, and neuropathologic
information to indicate a diagnosis of a superimposed inflammatory
polyneuropathy; nerve biopsy demonstrated excess lymphocytic
infiltration. Although it is clear that coexistent inflammatory neuropathy
is not genotype-specific in CMT, estimates of the prevalence of CMT disease
and inflammatory polyneuropathy may indicate that the association
is more frequent than would be expected by chance alone. This association
further implicates the immune system as a possible modulator in
the pathogenesis of both inflammatory neuropathies and CMT. Whether
treatment with steroids or immunoglobulin is effective in patients with
CMT who experience acute deterioration remains to be definitively studied;
there are not yet enough data to make a firm recommendation.
Because oxidative stress is considered a pathogenic factor in most models of
neurodegeneration, antioxidants have long been considered a viable pharmacologic
target in progressive neurologic diseases. However, it remains to be
seen whether antioxidant compounds could have a significant, long-term,
disease-modifying effect in CMT. Before these compounds can be recommended,
randomized, placebo-controlled trials are needed to explore the
efficacy of antioxidants such as vitamins E and C, coenzyme Q10, selegiline,
beta carotene, lipoic acid, N-acetylcysteine, and N-carboxymethyllysine.
These agents are thought to be generally harmless, which is a great advantage.
Other free-radical scavengers and antioxidants are still in the preclinical,
investigatory stage. Preclinical trials using an animal model show that
disabled mice force-fed with high doses of ascorbic acid partially recover
muscular strength after a few months of treatment, suggesting that high
doses of ascorbic acid repress PMP22 expression. A recent study by Kaya et
al. [35, Class II] demonstrated that ascorbic acid represses PMP22 gene expression
by acting on intracellular cAMP levels and adenylate cyclase activity.
This action was dose-dependent and appeared to be specific to ascorbic
acid; repression was not observed after treatment with other antioxidants.
Many myelin gene mutations appear to result in aberrant proteins that accumulate
primarily within the endoplasmic reticulum. This accumulation
in turn results in Schwann cell death by apoptosis with subsequent peripheral
neuropathy. Khajavi et al. [36, Class II] have shown that curcumin
supplementation can abrogate accumulation of aberrant protein products
in the endoplasmic reticulum and subsequent aggregation-induced
apoptosis, using a neuropathy model associated with myelin protein zero
(MPZ) mutants. Curcumin treatment reduced apoptosis of cells in tissue
culture expressing PMP22 mutants. Oral administration of curcumin also
appears to partially mitigate the severity of the Trembler–J mouse phenotype
in a dose-dependent manner [36, Class II]. Administration of curcumin
significantly decreased the percentage of apoptotic Schwann cells,
resulting in increased numbers and size of myelinated axons in sciatic
nerves. The cellular effects were shown to lead to improved functional
motor performance in this murine model of neuropathy.
100 Neuromuscular Disorders
The gene encoding the ganglioside-induced-differentiation-associated
protein 1 (GDAP1) has been associated with both demyelinating and
axonal phenotypes of CMT [37–39, Class II,III]. It is unknown whether
manipulating this gene or trying to replace it would modify the disease.
The protein encoded by GDAP1 is clearly similar to glutathione transferases;
it potentially could be created synthetically and replaced by
enzyme replacement therapy technology.
Sereda et al. [40, Class II] used a transgenic Pmp22 rat model to test
whether progesterone, a regulator of the myelin genes Pmp22 and MPZ in
cultured Schwann cells, can modulate the progression of the neuropathy.
Male transgenic rats were randomly given either progesterone, progesterone
antagonist (onapristone), or a placebo. Daily administration of
progesterone resulted in enhanced Schwann cell pathology and a more
severe clinical neuropathy. In contrast, administration of the selective
progesterone receptor antagonist resulted in reduction of Pmp22 expression
and a clinically improved CMT phenotype. These data provide some
evidence that the progesterone receptor of myelin-forming Schwann cells
is a promising pharmacologic target for treatment of CMT1A.
With increasing cognizance of the physiological functions of endogenous
and exogenous cannabinoids, it is becoming evident that they may be
involved in the pathology of some diseases, particularly neuromuscular
disorders. Cannabinoids may induce proliferation, growth arrest, or
apoptosis in a number of cells, including neurons, lymphocytes, and
various transformed neural and nonneural cells [41,42, Class II,III].
Most experimental evidence indicates that cannabinoids may protect
neurons in the central nervous system from toxic insults such as glutamatergic
overstimulation, ischemia, and oxidative damage [43–45,
Class II]. The neuroprotective effect of cannabinoids may have potential
clinical relevance for the treatment of neurodegenerative disorders
such as CMT. Both endogenous and exogenous cannabinoids appear
to have neuroprotective and antioxidant effects. Recent studies have
demonstrated the neuroprotective effects of synthetic, nonpsychotropic
cannabinoids, which appear to protect neurons from chemically induced
excitotoxicity. Direct measurement of oxidative stress reveals that cannabinoids
prevent cell death through antioxidation. The antioxidative
property of cannabinoids is confirmed by their ability to antagonize oxidative
stress and consequent cell death induced by the powerful oxidant,
retinoid anhydroretinol. Cannabinoids also modulate cell survival and
growth of B lymphocytes and fibroblasts [45, Class II].
In a murine model of experimental allergic neuritis, cannabinoids
showed efficacy as immune modulators [45, Class II].
No potential conflicts of interest relevant to this article were reported. Studies performed
by the authors of this manuscript are supported by a Research and Training Center Grant
from the National Institute on Disability and Rehabilitation Research #HB133B98008 and
a Project Grant from the National Institutes of Health #2P01HB33988-064A1.
Charcot-Marie-Tooth Disease Carter et al. 101
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Papers of particular interest, published recently,
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• Of importance
•• Of major importance
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