Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary neuropathies are classified into Charcot-Marie-Tooth disease (CMT), familial amyloid polyneuropathy (FAP), hereditary motor neuropathies (HMN) and hereditary sensory (and autonomic) neuropathies (HSAN). CMTs are furthermore classified into demyelinating neuropathies (CMT1), axonal neuropathies (CMT2) and intermediate form. Duplication of PMP22 (CMT1A) accounts for about 70% of CMT1 and MFN2 mutations account for 25% of CMT2. Genes involved in phosphoinositide regulation cause CMT4; MTMR2 mutation in CMT 4B1 and MTMR13/SBF2 mutation in CMT4B2. In addition to these genes, FIG4, which is a causative gene of pale tremor mouse, is newly identified as a gene for CMT4J. MFN2 and GDAP1 cause CMT2 or CMT4. These genes regulate mitochondrial fusion and fission. Altered axonal mitochondrial transport is suggested as the pathogenesis of the CMT. In animal model with pmp22 duplication, ascorbic acid seems to be effective to prevent disease progression. Nationwide trial of ascorbic acid therapy for CMT1A is now ongoing by the intractable neuropathy study group. Curcumin treatment educes apoptosis of cells that express PMP22 point mutation and partially mitigates the severe neuropathy phenotype of Trembler-J mouse model in a dose-dependent manner. Curcumin treatment may have a potential therapeutic role in CMT with PMP22 point mutation in humans. The high throughput system of diagnosis for CMT has been developed by employing a resequencing array system.
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PMID:[Hereditary neuropathy: recent advance]. 1919 50

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy and is a genetically and clinically heterogeneous disorder. We examined a Korean family in which two individuals had an autosomal-dominant axonal CMT with early-onset, sensory ataxia, tremor, and slow disease progression. Pedigree analysis and exome sequencing identified a de novo missense mutation (p.Y223H) in the diacylglycerol O-acyltransferase 2 (DGAT2) gene. DGAT2 encodes an endoplasmic reticulum-mitochondrial-associated membrane protein, acyl-CoA:diacylglycerol acyltransferase, which catalyzes the final step of the triglyceride (TG) biosynthesis pathway. The patient showed consistently decreased serum TG levels, and overexpression of the mutant DGAT2 significantly inhibited the proliferation of mouse motor neuron cells. Moreover, the variant form of human DGAT2 inhibited the axonal branching in the peripheral nervous system of zebrafish. We suggest that mutation of DGAT2 is the novel underlying cause of an autosomal-dominant axonal CMT2 neuropathy. This study will help provide a better understanding of the pathophysiology of axonal CMT and contribute to the molecular diagnostics of peripheral neuropathies.
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PMID:DGAT2 Mutation in a Family with Autosomal-Dominant Early-Onset Axonal Charcot-Marie-Tooth Disease. 2678 38