scholarly journals Atypical presentation of Charcot-Marie-Tooth disease type 1C with a new mutation: a case report

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Monika Turčanová Koprušáková ◽  
Milan Grofik ◽  
Ema Kantorová ◽  
Petra Jungová ◽  
Ján Chandoga ◽  
...  
Keyword(s):  
New Mutation ◽  
Gene Encoding ◽  
Case Presentation ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Inflammatory Neuropathy ◽  
Inherited Neuropathies ◽  
Partial Effects ◽  
Progressive Weakness ◽  
Tooth Disease

Abstract Background Charcot-Marie-Tooth 1C (CMT1C) is a rare form of dominantly inherited CMT1 neuropathy caused by a mutated gene encoding lipopolysaccharide-induced tumour necrosis alpha factor (LITAF). Case presentation We report a 56-year-old patient with an atypical clinical phenotype of CMT1C, which started as progressive weakness of a single upper limb resembling acquired inflammatory neuropathy. Nerve conduction studies (NCS) and temporarily limited and partial effects of immunotherapy supported the diagnosis of inflammatory neuropathy. Significant progression of polyneuropathy, despite intensive long-lasting immunotherapy, together with repeatedly negative auxiliary investigations (CSF, MRI and antibodies) and genetic testing results finally led to the diagnosis of CMT1C neuropathy. Conclusions CMT1C should be added to the list of inherited neuropathies that need to be considered in suspected cases of inflammatory demyelinating neuropathy.

scholarly journals A murine model of Charcot-Marie-Tooth disease 4F reveals a role for the C-terminus of periaxin in the formation and stabilization of Cajal bands

2018 ◽  
Vol 3 ◽  
pp. 20 ◽  
Author(s):  
Diane L. Sherman ◽  
Peter J. Brophy
Keyword(s):  
Plasma Membrane ◽  
Schwann Cell ◽  
Laminin Receptor ◽  
Cell Plasma Membrane ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
C Terminus ◽  
Cell Plasma ◽  
Inherited Neuropathies ◽  
Tooth Disease

Charcot-Marie-Tooth (CMT) disease comprises up to 80 monogenic inherited neuropathies of the peripheral nervous system (PNS) that collectively result in demyelination and axon degeneration. The majority of CMT disease is primarily either dysmyelinating or demyelinating in which mutations affect the ability of Schwann cells to either assemble or stabilize peripheral nerve myelin. CMT4F is a recessive demyelinating form of the disease caused by mutations in the Periaxin (PRX) gene. Periaxin (Prx) interacts with Dystrophin Related Protein 2 (Drp2) in an adhesion complex with the laminin receptor Dystroglycan (Dag). In mice the Prx/Drp2/Dag complex assembles adhesive domains at the interface between the abaxonal surface of the myelin sheath and the cytoplasmic surface of the Schwann cell plasma membrane. Assembly of these appositions causes the formation of cytoplasmic channels called Cajal bands beneath the surface of the Schwann cell plasma membrane. Loss of either Periaxin or Drp2 disrupts the appositions and causes CMT in both mouse and man. In a mouse model of CMT4F, complete loss of Periaxin first prevents normal Schwann cell elongation resulting in abnormally short internodal distances which can reduce nerve conduction velocity, and subsequently precipitates demyelination. Distinct functional domains responsible for Periaxin homodimerization and interaction with Drp2 to form the Prx/Drp2/Dag complex have been identified at the N-terminus of Periaxin. However, CMT4F can also be caused by a mutation that results in the truncation of Periaxin at the extreme C-terminus with the loss of 391 amino acids. By modelling this in mice, we show that loss of the C-terminus of Periaxin results in a surprising reduction in Drp2. This would be predicted to cause the observed instability of both appositions and myelin, and contribute significantly to the clinical phenotype in CMT4F.

Quantitative measurement of duplicated DNA as a diagnostic test for Charcot-Marie-Tooth disease type 1a

1993 ◽  
Vol 39 (9) ◽  
pp. 1845-1849 ◽  
Author(s):  
G W Hensels ◽  
E A Janssen ◽  
J E Hoogendijk ◽  
L J Valentijn ◽  
F Baas ◽  
...  
Keyword(s):  
Preliminary Investigation ◽  
Sensory Neuropathy ◽  
Disease Type ◽  
Chromosome 17 ◽  
Hereditary Neuropathy ◽  
Chromosomal Dna ◽  
Gene Encoding ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

Abstract Charcot-Marie-Tooth disease type 1 (CMT1) is a hereditary motor and sensory neuropathy. The autosomal dominant subtype is often linked with a large duplication on chromosome 17p11.2. The gene encoding the peripheral myelin protein PMP 22 (the critical gene in this subtype of CMT1) is located within this duplication. To detect this duplication in chromosomal DNA from individuals thought to have CMT1, we compared the hybridization signals of two DNA probes within this duplication (VAW412R3a and VAW409R3a) with the signal of a reference probe (E3.9). When duplication was present, the signals from the first two probes increased from 100% (for nonduplicated samples) to 145% and 142%, respectively. The day-to-day variance was 3.7% and 5.1%, respectively. We demonstrated this DNA duplication in 49 of 95 DNA samples from unrelated individuals thought to have CMT1. Moreover, because hereditary neuropathy with liability to pressure palsies (HNPP) is based on a DNA deletion in the same area of chromosome 17, this quantitative test may be useful in establishing the presence of HNPP. In a preliminary investigation, four unrelated patients with HNPP yielded test values of 63% and 54%, respectively, of those for nonduplicated samples (CV 19% and 18%, respectively; n = 4), suggesting a deletion in 17p11.2.

scholarly journals Mutation in the Gene Encoding Ubiquitin Ligase LRSAM1 in Patients with Charcot-Marie-Tooth Disease

PLoS Genetics ◽  
2010 ◽  
Vol 6 (8) ◽  
pp. e1001081 ◽  
Author(s):  
Duane L. Guernsey ◽  
Haiyan Jiang ◽  
Karen Bedard ◽  
Susan C. Evans ◽  
Meghan Ferguson ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Gene Encoding ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

P3.23 Characterization of a new mutation in the GADP1 gene causing axonal autosomal dominant Charcot-Marie-Tooth disease (CMT2K)

2011 ◽  
Vol 21 (9-10) ◽  
pp. 688-689
Author(s):  
M. Guijarro ◽  
P. Blanco-Arias ◽  
J. Pardo ◽  
C. Concheiro-Álvarez ◽  
B. San Millán ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
New Mutation ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

The phenotype of Charcot–Marie–Tooth disease type 4C due to SH3TC2 mutations and possible predisposition to an inflammatory neuropathy

2009 ◽  
Vol 19 (4) ◽  
pp. 264-269 ◽  
Author(s):  
Henry Houlden ◽  
Matilde Laura ◽  
Lionel Ginsberg ◽  
Heinz Jungbluth ◽  
Stephanie A. Robb ◽  
...  
Keyword(s):  
Disease Type ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Inflammatory Neuropathy ◽  
Tooth Disease

scholarly journals PROGRESS IN CLINICAL NEUROSCIENCES: Charcot-Marie-Tooth Disease and Related Inherited Peripheral Neuropathies

2001 ◽  
Vol 28 (3) ◽  
pp. 199-214 ◽  
Author(s):  
Timothy J. Benstead ◽  
Ian A. Grant
Keyword(s):  
Molecular Genetic ◽  
Charcot Marie Tooth ◽  
Hereditary Motor ◽  
Charcot Marie Tooth Disease ◽  
Inherited Neuropathy ◽  
Molecular Aspects ◽  
The Many ◽  
Inherited Neuropathies ◽  
Tooth Disease

The classification of Charcot-Marie-Tooth disease and related hereditary motor and sensory neuropathies has evolved to incorporate clinical, electrophysiological and burgeoning molecular genetic information that characterize the many disorders. For several inherited neuropathies, the gene product abnormality is known and for others, candidate genes have been identified. Genetic testing can pinpoint a specific inherited neuropathy for many patients. However, clinical and electrophysiological assessments continue to be essential tools for diagnosis and management of this disease group. This article reviews clinical, electrophysiological, pathological and molecular aspects of hereditary motor and sensory neuropathies.

A new mutation of the Po gene in patients with Charcot-Marie-Tooth disease type 1B: screening of the Po gene by heteroduplex analysis

1996 ◽  
Vol 204 (3) ◽  
pp. 173-176 ◽  
Author(s):  
Nobutada Tachi ◽  
Naoki Kozuka ◽  
Kazuhiro Ohya ◽  
Shunzo Chiba ◽  
Kimio Sasaki ◽  
...  
Keyword(s):  
Disease Type ◽  
Heteroduplex Analysis ◽  
New Mutation ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

scholarly journals DHTKD1 deficiency causes Charcot-Marie-Tooth disease in mice

2018 ◽  
pp. MCB.00085-18 ◽  
Author(s):  
Wang-Yang Xu ◽  
Houbao Zhu ◽  
Yan Shen ◽  
Ying-Han Wan ◽  
Xiao-Die Tu ◽  
...  
Keyword(s):  
Insulin Biosynthesis ◽  
Charcot Marie Tooth ◽  
Structure Damage ◽  
Early Growth Response ◽  
Charcot Marie Tooth Disease ◽  
Tryptophan Catabolism ◽  
Protein Zero ◽  
Progressive Weakness ◽  
Tooth Disease

DHTKD1, a part of 2-ketoadipic acid dehydrogenase complex, is involved in lysine and tryptophan catabolism. Mutations in DHTKD1 block the metabolic pathway and cause 2-aminoadipic and 2-oxoadipic aciduria (AMOXAD), an autosomal recessive inborn metabolic disorder. In addition, a nonsense mutation in DHTKD1 we identified previously causes Charcot-Marie-Tooth disease (CMT) type 2Q, one of the most common inherited neurological disorders affecting the peripheral nerves in the musculature. However, the comprehensive molecular mechanism underlying CMT2Q remains elusive. Here we show that Dhtkd1-/- mice mimic the major aspects of CMT2 phenotypes, featured by progressive weakness and atrophy in the distal parts of limbs with motor and sensory dysfunctions, which are accompanied with decreased nerve conduction velocity. Moreover, Dhtkd1-deficiency causes severe metabolic abnormalities and dramatically increased levels of 2-ketoadipic acid (2-KAA) and 2-aminoadipic acid (2-AAA) in urine. Further studies reveal that both 2-KAA and 2-AAA could stimulate insulin biosynthesis and secretion. Subsequently, elevated insulin regulates myelin protein zero (Mpz) transcription in Schwann cells via upregulating the expression of early growth response 2 (Egr2), leading to myelin structure damage and axonal degeneration. Finally, 2-AAA-fed mice do reproduce the phenotypes like CMT2Q. In conclusion, we have demonstrated that loss of Dhtkd1 causes CMT2Q-like phenotypes through dysregulation of Mpz mRNA and P0 protein closely-associated with elevated DHTKD1 substrate and insulin levels. These findings further implicate an important role of metabolic disorders in addition to mitochondrial insufficiency in the pathogenesis of peripheral neuropathies.

Sign in / Sign up

Export Citation Format

Share Document