Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0152025 (polyneuropathy)
 7,862 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (OMIM 218000) is an autosomal recessive disease of early onset characterized by a delay in developmental milestones, a severe sensory-motor polyneuropathy with areflexia, a variable degree of agenesis of the corpus callosum, amyotrophy, hypotonia, and cognitive impairment. Although this disorder has rarely been reported worldwide, it has a high prevalence in the Saguenay-Lac-St-Jean region of the province of Quebec (Canada) predominantly because of a founder effect. The gene defect responsible for this disorder recently has been identified, and it is a protein-truncating mutation in the SLC12A6 gene, which codes for a cotransporter protein known as KCC3. Herein, we provide the first extensive review of this disorder, covering epidemiological, clinical, and molecular genetic studies.
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PMID:Hereditary motor and sensory neuropathy with agenesis of the corpus callosum. 1283 16

The causes of epilepsies and epileptic seizures are multifactorial. Genetic predisposition may contribute in certain types of epilepsies and seizures, whether idiopathic or symptomatic of genetic origin. Although these are not very common, they have offered a unique opportunity to investigate the molecular mechanisms underlying epileptogenesis and ictogenesis. Among the implicated gene mutations, a number of GABAA receptor subunit mutations have been recently identified that contribute to several idiopathic epilepsies, febrile seizures, and rarely to certain types of symptomatic epilepsies, like the severe myoclonic epilepsy of infancy. Deletion of GABAA receptor genes has also been linked to Angelman syndrome. Furthermore, mutations of proteins controlling chloride homeostasis, which indirectly defines the functional consequences of GABAA signaling, have been identified. These include the chloride channel 2 (CLCN2) and the potassium chloride cotransporter KCC3. The pathogenic role of CLCN2 mutations has not been clearly demonstrated and may represent either susceptibility genes or, in certain cases, innocuous polymorphisms. KCC3 mutations have been associated with hereditary motor and sensory polyneuropathy with corpus callosum agenesis (Andermann syndrome) that often manifests with epileptic seizures. This review summarizes the recent progress in the genetic linkages of epilepsies and seizures to the above genes and discusses potential pathogenic mechanisms that contribute to the age, sex, and conditional expression of these seizures in carriers of these mutations.
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PMID:Mutations affecting GABAergic signaling in seizures and epilepsy. 2035 46

Hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (HMSN/ACC) is an autosomal recessive disease of the central and peripheral nervous system that presents as early-onset polyneuropathy. Patients are hypotonic and areflexic from birth, with abnormal facial features and atrophic muscles. Progressive peripheral neuropathy eventually confines them to a wheelchair in the second decade of life, and death occurs by the fourth decade. We here define the neuropathologic features of the disease in autopsy tissues from eight cases. Both developmental and neurodegenerative features were found. Hypoplasia or absence of the major telencephalic commissures and a hypoplasia of corticospinal tracts to half the normal size, were the major neurodevelopmental defects we observed. Despite being a neurodegenerative disease, preservation of brain weight and a conspicuous absence of neuronal or glial cell death were signal features of this disease. Small tumor-like overgrowths of axons, termed axonomas, were found in the central and peripheral nervous system, indicating attempted axonal regeneration. We conclude that the neurodegenerative deficits in HMSN/ACC are primarily caused by an axonopathy superimposed upon abnormal development, affecting peripheral but also central nervous system axons, all ultimately because of a genetic defect in the axonal cotransporter KCC3.
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PMID:KCC3 axonopathy: neuropathological features in the central and peripheral nervous system. 2723 Apr 13