Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007758 (cerebellar ataxia)
 3,609 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebellar vermis aplasia (ACV, OMIM 117360) is a rare malformation of the cerebellum, with only few familial patients reported so far. Main clinical features of this rare disorder include floppiness and delayed milestones in early infancy, preceding mild cerebellar ataxia, non-progressive clinical course, normal or slightly delayed intelligence, and occasional nystagmus. Neuroimaging reveals selective involvement of the cerebellum, which is prominent in the vermis. Because of the large preponderance of female patients, X-linked dominant transmission was suggested by [Fenichel and Phillips (1989); Arch Neurol 46:582-583], and subsequent reports only concern female patients. Only one family with male-to-male transmission presenting with a generalized atrophy of the cerebellum rather than a more localized vermis aplasia has been reported so far. We report on a family in which father and son are affected by a mild form of ACV, thus confirming an autosomal mode of inheritance of the disease. Our patients showed a progressive improvement of their motor abilities, neurological examination of the father being actually normal except for a mild mental retardation. We also evaluated the potential role of two candidate genes, EN2 and ZIC1, responsible for abnormal cerebellar development in murine knock-out models. However, molecular analysis failed to reveal any causative mutation in the coding sequence of the two genes in our patients. The understanding of the genetic basis of autosomal dominant ACV would allow a better classification of isolate cerebellar malformations and might permit to understand cell differentiation and migration in the developing central nervous system.
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PMID:Cerebellar vermis aplasia: patient report and exclusion of the candidate genes EN2 and ZIC1. 1594 Jun 96

We review the neuronal antibodies described in CNS disorders in order to clarify their diagnostic value, emphasize potentials pitfalls and limitations in the diagnosis of paraneoplastic neurological syndromes (PNS), and examine the current evidence for a possible pathogenic role. We propose to classify the neuronal antibodies associated with syndromes resulting from CNS neuronal dysfunction into two groups according to the location of the antigen: inside the neuron or in the cell membrane. Group I includes antibodies which target intracellular antigens and probably are not pathogenic. They are further subdivided into three groups. Group Ia comprises well-characterized onconeural antibodies (Hu (ANNA1), Yo (PCA1), Ri (ANNA2), CV2 (CRMP5), amphiphysin, Ma2) that are useful for the diagnosis of PNS. Group Ib antibodies (SOX and ZIC) are cancer-specific but there is no evidence that the immune response is in any way pathogenically related to the PNS. Antibodies in group Ic (glutamic acid decarboxylase (GAD), adenylate kinase 5 and Homer 3) identify non-PNS: stiff-person syndrome (SPS), cerebellar ataxia, and limbic encephalitis (LE). Group II antibodies recognize neuronal surface antigens. Antibodies in group IIa associate with characteristic CNS syndromes but their detection does not indicate that the disorder is paraneoplastic. Antibodies to potassium channels, AMPA and GABA(B) receptors are associated with LE, NMDA receptor antibodies identify a well-defined encephalitis, and antibodies against glycine receptors associate with SPS with encephalitis. A pathogenic role of the antibodies is suggested by the response of symptoms to immunotherapy and the correlation between antibody titers and neurological outcome. Lastly, Group IIb includes antibodies that are found in patients with paraneoplastic cerebellar ataxia associated with lung cancer (P/Q type calcium channels antibodies) or Hodgkin disease (metabotropic glutamate receptor type 1 antibodies).
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PMID:Antibodies and neuronal autoimmune disorders of the CNS. 2003 30

Various autoantibodies are associated with autoimmune-mediated cerebellar ataxia. Anti-Yo, -Zic, -CARPVIII, -Tr, -Ri, -Hu, -Ma, -CRMP-5, -ANNA-3, -PCA-2, -VGCC, and -mGluR antibodies (Abs) are found in paraneoplastic cerebellar ataxia, whereas anti-GAD, -thyroid, and -gliadin Abs are found in non-paraneoplastic cerebellar ataxia. Most of these antibodies are not pathogenic but are diagnostic markers. However, anti-VGCC, anti-mGluR, and anti-GAD Abs have been shown to cause cerebellar ataxia, because administration of these Abs mimics cerebellar ataxia in vivo. Experiments using in vitro preparations show that anti-VGCC Ab depresses excitatory synaptic transmissions, and anti-GAD Ab suppresses inhibitory synaptic transmissions. Anti-mGluR Ab interferes with the induction of synaptic plasticity. These results suggest that pathogenic Abs elicit cerebellar synaptic dysfunction, and thereby cause ataxia in patients.
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PMID:[Autoantibodies associated with autoimmune-mediated cerebellar ataxia]. 2356 83