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Hereditary Neuropathy (hereditary + neuropathy)

Distribution by Scientific Domains

Medical Sciences	87%
Life Sciences	12%

Selected Abstracts

Hereditary neuropathy with liability to pressure palsies associated with central nervous system myelin lesions

EUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2001
J. Dac
Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder most commonly caused by a 1.5-Mb deletion in chromosome 17p11.2 which contains the peripheral myelin protein-22 (PMP22) gene. Mutations resulting in functional loss of one PMP22 gene copy are less frequent. We present a 51-year-old patient with a l.5-Mb deletion in chromosome 17p11.2 who exhibited signs of peripheral as well as central nervous system lesions. He gave a history of recurrent episodes of limb numbness and weakness with spontaneous but incomplete recovery since age 20. His father and two brothers had similar symptoms. Neurological examination revealed signs of multiple mononeuropathy associated with frontal lobe, corticospinal tract and cerebellar dysfunction, as well as signs of initial cognitive impairment. Electrophysiological investigations showed a demyelinating peripheral nerve disease with multiple conduction blocks and conduction disturbances in both optic nerves. Magnetic resonance imaging of the brain revealed multiple subcortical and periventricular foci of myelin lesions. The association of central and peripheral nervous system lesions in this patient indicates a possible role of PMP22 not only in peripheral but also in central nervous system myelin structure. [source]

Hereditary neuropathy with liability to pressure palsies and anaesthesia: peri-operative nerve injury

ANAESTHESIA, Issue 10 2006
L. Wijayasiri
Summary A 43-year-old female with carcinoma of the left breast underwent wide local excision of the tumour and sentinel lymph node biopsy under general anaesthesia. Three lymph nodes were removed uneventfully during the operation. Postoperatively, the patient complained of weakness and decreased sensation of her left arm. A diagnosis of peri-operative neuropraxia was made. This resolved completely over the following 4 weeks. Genetic testing confirmed a diagnosis of hereditary neuropathy with liability to pressure palsies. [source]

Electrophysiological features in the distinction between hereditary demyelinating and chronic acquired demyelinating neuropathies

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004
F Poglio
We carried out an electrophysiological retrospective study in 55 patients with chronic demyelinating acquired and hereditary neuropathies. Alterations of motor nerve conduction velocities (MNCV), distal motor latencies (DML), conduction blocks (CB) and compound muscle action potential (CMAP) were compared, considering the whole number of nerves for each disease. MNCV, DML, CB and CMAP were considered suggestive of demyelination when meeting the American Academy of Neurology (AAN) criteria. Abnormally slow MNCV was found respectively in the 46% of all the CMTX female nerves studied, in the 56.5% of CMTX males, 84% of CMT1A, 74% CIDP and 70% of MAG-PNP. Prolonged DML was observed in the 25% of the CMTX female nerves studied, in the 49.5% of CMTX males, 81% of CMT1A, 63% of CIDP and 71% of MAG-PNP. Moreover, CB were quite often evidenced in CIDP and MAG-PNP nerves (respectively in 48% and 29%) and rarely in hereditary neuropathies. Finally, we observed CMAP reduction in the 45% of all the CMTX female nerves studied, in the 50% of CMTX males, 63% of CMT1A, 49% of CIDP and 60% of MAG-PNP. A well-characterized pattern generally allows an electrophysiological distinction between CMT1A, CMTX males, MAG-PNP on one side and CIDP and CMTX females on the other side. A clear electrodiagnostic distinction result is often hard between CMTX males and MAG-PNP and between CIDP and CMTX females. [source]

BONE MARROW TRANSFER FROM WILD-TYPE MICE REVERTS THE BENEFICIAL EFFECT OF GENETICALLY MEDIATED IMMUNE DEFICIENCY IN MYELIN MUTANTS

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2002
M Maurer
Inherited demyelinating neuropathies are chronically disabling human disorders caused by various genetic defects, including deletions, single site mutations, and duplications in the respective myelin genes. We have shown in a mouse model of one distinct hereditary demyelinating neuropathy (heterozygous PO-deficiency, PO±) that an additional null mutation in the recombination activating gene-1 (RAG-1--) leads to a substantially milder disorder, indicating a disease modifying role of T-lymphocytes. In the present study, we addressed the role of lymphocytes in the mouse model by reconstituting bone marrow of PO±/RAG-1-- mice with bone marrow from immunocompetent wild-type mice. We compared the pathology and nerve conduction in double mutant mice (PO±/RAG-1-- on a C57BL/6 background) with that in double mutants after receiving a bone marrow transplant. We found that the milder demyelination seen in the lymphocyte-deficient PO±/RAG-1-- mutants was reverted to the more severe pathology by reestablishing a competent immune system by bone marrow transfer. These data corroborate the concept that the immune system contributes substantially to the pathologic process in this mouse model and may open new avenues to ameliorate human hereditary neuropathies by exploiting immunosuppressive treatments. [source]

Novel MPZ Mutation In A Sporadic CMT Patient

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001
E Bellone
Mutations in the gene for the major structural protein component of peripheral nerve myelin, myelin protein zero (MPZ), are associated with some forms of hereditary neuropathies such as Charcot-Marie-Tooth disease type 1B (CMT1B), Dejerine-Sottas syndrome (DSS) and congenital hypomyelinating neuropathy (CHN). The common pathological characteristics of these allelic disorders are severe demyelination and remyelination of peripheral nerves. Recently, MPZ mutations were also found in patients with the axonal form of CMT neuropathy (CMT2). We studied a patient with negative familiar history and clinical and electrophysiological features of Charcot-Marie-Tooth disease: distal muscle weakness and atrophy, foot deformities (pes cavus), and severely reduced nerve conduction velocities in the motor and sensory nerves. The sural nerve biopsy showed marked loss of myelinated fibers, few onion bulbs, and a high percentage of fibers showing excessive myelin outfoldings. DNA analysis excluded CMT1A duplication by Southern blot and by pulsed field gel electrophoresis methods. SSCP analysis of all six exons of MPZ revealed a shift band in exon 2 in the patient's DNA. No such difference was detected in normal controls. Direct sequencing disclosed a G , A transition at nucleotide position 181. This base substitution predicts the replacement of aspartic acid with asparagine at codon 61. A mutation at the same codon (but different amino acid replacement) was recently identified in a family with the axonal type of CMT, in which the disease was autosomal dominantly inherited. This finding provides further confirmation of the role of MPZ gene in peripheral neuropathies and suggests that MPZ coding region mutations may account for a considerable number of CMT cases which do not involve DNA duplication on 17p11.2-p12. This research was partially supported by a MURST and an Ateneo grant to FA, by a Ministero della Sanità grant to PM. Our laboratory is a member of the European Charcot-Marie-Tooth Consortium co-ordinated by Prof. Christine Van Broeckhoven. [source]

Enhanced B7 Costimulatory Molecule Expression In Inflammatory Human Sural Nerve Biopsies

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001
R Kiefer
Objectives-To define the role of the costimulatory molecules B7-1 and B7-2 in inflammatory disorders of the peripheral nervous system. B7 molecules are essential for effective antigen presentation and may determine the differentiation of T cells into a Th-1 or Th-2 phenotype, thus modulating immune response and disease course. Methods-Forty nine sural nerve biopsies from patients with neuroborreliosis, Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), CIDP variants and hereditary neuropathies, and those with no detectable abnormality were investigated. The expression of B7-1 and B7-2 mRNA and protein was investigated by polymerase chain reaction (PCR) and immunocytochemistry. Results-B7-1 mRNA was strongly upregulated in both cases of neuroborreliosis, in two cases of GBS and one case of variant CIDP. Moderate to low levels were detected in the remaining GBS and CIDP biopsies and were rarely found in a noninflammatory control group consisting of hereditary neuropathy and normal nerves. At the immunocytochemical level, strong expression of B7-1 protein was found in both neuroborreliosis cases, and moderate or low expression in six of eight GBS cases and seven of 17 CIDP cases investigated, whereas only one of five non-inflammatory control nerves showed staining, which was very weak. In neuroborreliosis, B7-1 protein was found very pronounced in epineurial infiltrates, whereas in CBS and CIDP, labelling was predominantly endoneurial and localised to putative macrophages. B7-2 mRNA and protein were expressed only at low levels in neuroborreliosis and selected autoimmune neuropathy cases, and were essentially absent from noninflammatory controls. Conclusions-B7 molecules are expressed in the peripheral nervous system and regulated during disease, and their presence in macrophages underlines the putative function of endoneurial macrophages as local antigen presenting cells in the immunopathology of peripheral nerve. B7-1 rather than B7-2 is preferentially upregulated, possibly promoting the induction of a Th-1-type T cell response within the nerve. [source]

The dominantly inherited motor and sensory neuropathies: Clinical and molecular advances

MUSCLE AND NERVE, Issue 5 2006
Garth A. Nicholson MB
Abstract The rapid advances in the molecular genetics and cell biology of hereditary neuropathy have revealed great genetic complexity. It is a challenge for physicians and laboratories to keep pace with new discoveries. Classification of hereditary neuropathies has evolved from a simple clinical to a detailed molecular classification. However, the molecular classification is not simple to use, as different mutations of the same gene produce a range of phenotypes. The logistics of testing for multiple gene mutations are considerable. This review gives a clinical overview of molecular and clinical advances in the dominant hereditary motor and sensory neuropathies [HMSNs, Charcot,Marie,Tooth (CMT) neuropathy], which account for some 60%,70% of families with CMT. The dominant forms of CMT have cellular mechanisms different from those of recessive forms and are a separate diagnostic challenge, so they are not included in this review. Diagnostic testing requires accurate clinical information and a selective approach to gene screening until the cost of multiple gene mutation screening falls. Accurate molecular diagnosis is critical to genetic counseling. This review concentrates on how molecular information can be used clinically, on how physicians can keep pace with new developments, and on the relevance of this new knowledge to patients. Muscle Nerve, 2006 [source]

Lesion of the anterior branch of axillary nerve in a patient with hereditary neuropathy with liability to pressure palsies

EUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2000
S. Simonetti
We report the case of a 30-year-old woman affected by hereditary neuropathy with liability to pressure palsies (HNPP), who developed a painless left axillary neuropathy after sleeping on her left side, on a firm orthopaedic mattress, in her eighth month of pregnancy. Electromyography (EMG) showing neurogenic signs in the left anterior and middle deltoid, and normal findings in the left teres minor, posterior deltoid and other proximal upper limb muscles, demonstrated that the lesion was at the level of the axillary anterior branch. A direct compression of this branch against the surgical neck of the humerus seems the most likely pathogenic mechanism. This is the first documented description of an axillary neuropathy in HNPP. Knowledge of its possible occurrence may be important for prevention purposes. [source]

Peripheral myelin protein 22 is regulated post-transcriptionally by miRNA-29a,

GLIA, Issue 12 2009
Jonathan D. Verrier
Abstract Peripheral myelin protein 22 (PMP22) is a dose-sensitive, disease-associated protein primarily expressed in myelinating Schwann cells. Either reduction or overproduction of PMP22 can result in hereditary neuropathy, suggesting a requirement for correct protein expression for peripheral nerve biology. PMP22 is post-transcriptionally regulated and the 3,untranslated region (3,UTR) of the gene exerts a negative effect on translation. MicroRNAs (miRNAs) are small regulatory molecules that function at a post-transcriptional level by targeting the 3,UTR in a reverse complementary manner. We used cultured Schwann cells to demonstrate that alterations in the miRNA biogenesis pathway affect PMP22 levels, and endogenous PMP22 is subjected to miRNA regulation. GW-body formation, the proposed cytoplasmic site for miRNA-mediated repression, and Dicer expression, an RNase III family ribonuclease involved in miRNA biogenesis, are co-regulated with the differentiation state of Schwann cells. Furthermore, the levels of Dicer inversely correlate with PMP22, while the inhibition of Dicer leads to elevated PMP22. Microarray analysis of actively proliferating and differentiated Schwann cells, in conjunction with bioinformatics programs, identified several candidate PMP22-targeting miRNAs. Here we demonstrate that miR-29a binds and inhibits PMP22 reporter expression through a specific miRNA seed binding region. Over-expression of miR-29a enhances the association of PMP22 RNA with Argonaute 2, a protein involved in miRNA function, and reduces the steady-state levels of PMP22. In contrast, inhibition of endogenous miR-29a relieves the miRNA-mediated repression of PMP22. Correlation analyses of miR-29 and PMP22 in sciatic nerves reveal an inverse relationship, both developmentally and in post-crush injury. These results identify PMP22 as a target of miRNAs and suggest that myelin gene expression by Schwann cells is regulated by miRNAs. © 2009 Wiley-Liss, Inc. [source]

Ultrasonographic Reference Values for Assessing the Normal Median Nerve in Adults

JOURNAL OF NEUROIMAGING, Issue 1 2009
Michael S. Cartwright MD
ABSTRACT BACKGROUND AND PURPOSE Several studies have evaluated the cross-sectional area of the median nerve at the wrist, but none have examined other sites along the median nerve. Nerve enlargement has been demonstrated in entrapment, hereditary and acquired neuropathies, as well as with intraneural masses, and cross-sectional area reference values at sites along the nerve will help in the evaluation of these conditions. In addition, muscle intrusion into the carpal tunnel has been implicated in carpal tunnel syndrome, but the normal amount of muscle intrusion has not been quantified. METHODS Fifty asymptomatic volunteers (100 arms) were evaluated to determine the mean cross-sectional area of the median nerve at 6 sites and the mean amount of muscle intruding into the carpal tunnel. RESULTS The cross-sectional area of the nerve was consistent along its course (7.5 to 9.8 mm2). The amount of muscle within the carpal tunnel varied greatly, with the mean area of flexor digitorum being 15.5 mm2 and lumbricals 13.5 mm2. CONCLUSIONS These reference values are necessary for advancing the field of neuromuscular ultrasound, because they facilitate studies of the median nerve in conditions such as entrapment, hereditary neuropathy, acquired neuropathy, and intraneural masses. [source]

Molecular alterations resulting from frameshift mutations in peripheral myelin protein 22: Implications for neuropathy severity

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2005
J.S. Johnson
Abstract Alterations in peripheral myelin protein 22 (PMP22) expression are associated with a heterogeneous group of hereditary demyelinating peripheral neuropathies. Two mutations at glycine 94, a single guanine insertion or deletion in PMP22, result in different reading frameshifts and, consequently, an extended G94fsX222 or a truncated G94fsX110 protein, respectively. Both of these autosomal dominant mutations alter the second half of PMP22 and yet are linked to clinical phenotypes with distinct severities. The G94fsX222 is associated with hereditary neuropathy with liability to pressure palsies, whereas G94fsX110 causes severe neuropathy diagnosed as Dejerine-Sottas disease or Charcot-Marie-Tooth disease type IA. To investigate the subcellular changes associated with the G94 frameshift mutations, we expressed epitope-tagged forms in primary rat Schwann cells. Biochemical and immunolabeling studies indicate that, unlike the wild-type protein, which is targeted for the plasma membrane, frameshift PMP22s are retained in the cell, prior to reaching the medial Golgi compartment. Similar to Wt-PMP22, both frameshift mutants are targeted for proteasomal degradation and accumulate in detergent-insoluble, ubiquitin-containing aggregates upon inhibition of this pathway. The extended frameshift PMP22 shows the ability to form spontaneous aggregates in the absence of proteasome inhibition. On the other hand, Schwann cells expressing the truncated protein proliferate at a significantly higher rate than Schwann cells expressing the wild-type or the extended PMP22. In summary, these results suggest that a greater potential for PMP22 aggregation is associated with a less severe phenotype, whereas dysregulation of Schwann cell proliferation is linked to severe neuropathy. © 2005 Wiley-Liss, Inc. [source]