Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153640 (Cerebellum)
 1,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spinocerebellar ataxia type 20 (SCA20) was reported in 2004 in a single Australian Anglo-Celtic pedigree. The phenotype is distinctive, with palatal tremor, and hypermetric saccades, and early dentate (but not pallidal) calcification in the absence of abnormalities of calcium metabolism. Dysarthria, rather than gait ataxia, was the initial symptom in most, and was typically conjoined with dysphonia, clinically resembling adductor spasmodic dysphonia. The onset of these speech abnormalities was abrupt in some cases. MRI scanning showed mild to moderate pancerebellar atrophy with dentate calcification, with olivary pseudohypertrophy in some cases, in the absence of other brainstem or cerebral changes. Nerve conduction studies were normal. Progression appeared to be slow. SCA20 is probably rare, as despite the distinctive phenotype, only this one pedigree has been described. The locus mapped to the pericentromeric region of chromosome 11 with a LOD score of 4.47, and its candidate region overlaps that of SCA5. It seems probable that these two SCAs may be separate genetic entities, on the basis of their divergent clinical features, but formal proof awaits discovery of one or both responsible genes.
Cerebellum 2005
PMID:Spinocerebellar ataxia type 20. 1589 61

The autosomal dominant cerebellar ataxias (ADCAs) are a genetically heterogeneous group of disorders. Clinical classification of the ADCAs into three types has facilitated defining phenotypes and in turn, linkage analysis, which has led to the discovery of 30 loci and 16 genes. The type III ADCAs are 'pure' spinocerebellar ataxias (SCA), those that appear to elude neurological features outside of the cerebellum. At present 3 ADCA type III SCA genes have been published, SCA5, SCA6, and SCA14, these three genes appear to have various roles suggesting involvement in both different and possibly overlapping neurodegenerative pathways. The known ADCAIII genes are thought to have such roles as involvement in signal transduction, cell proliferation, synaptic transmission, and channel regulation. Here we update readers on the current progress on SCA11 and the identification of the disease gene. We discuss the clinical, genetic, and pathological details of SCA11--a locus at chromosome 15q14-q21.3 in a Caucasian family of British ancestry. We also discuss the refining of this region, and methods used to prioritize the screening of the over 130 candidate genes in this genomic region.
Cerebellum 2008
PMID:Clinical and genetic analysis of spinocerebellar ataxia type 11. 1841 80

A family with late-onset autosomal dominant pure cerebellar ataxia, consistent with spinocerebellar ataxia type 5 (SCA5) but lacking previously reported SPTBN2 mutations, was identified. DNA was collected from seven individuals across two generations and the SPTBN2 gene on chromosome 11 was sequenced. A nonsynonymous heterozygous substitution in exon 12 was detected in individuals diagnosed with SCA5 while unaffected family members did not possess this variant. The identified c.1415C>T variant results in a p.T472M substitution in the second SPEC domain of the beta-III spectrin protein. The threonine at position 472 is not in close proximity to the characteristic residues that define the SPEC domain and is variable across diverse SPEC domains, yet is highly conserved in SPTBN2. Consistent with these observations, bioinformatic analysis of the p.T472M variant suggests it to be pathological. Two deletions within the SPTBN2 SPEC domains (E532_M544del and L629_R634delinsW) have been previously reported to cause SCA5, but this is the first missense mutation in this region of the protein shown to likely be pathogenic.
Cerebellum 2013 Apr
PMID:A family with spinocerebellar ataxia type 5 found to have a novel missense mutation within a SPTBN2 spectrin repeat. 2284 92

Chance discovery of spontaneous mutants with atrophy of the cerebellar cortex has unearthed genes involved in optimizing motor coordination. Rotorod, stationary beam, and suspended wire tests are useful in delineating behavioral phenotypes of spontaneous mutants with cerebellar atrophy such as Grid2Lc, Grid2ho, Rorasg, Agtpbp1pcd, Relnrl, and Dab1scm. Likewise, transgenic or null mutants serving as experimental models of spinocerebellar ataxia (SCA) are phenotyped with the same tests. Among experimental models of autosomal dominant SCA, rotorod deficits were reported in SCA1 to 3, SCA5 to 8, SCA14, SCA17, and SCA27 and stationary beam deficits in SCA1 to 3, SCA5, SCA6, SCA13, SCA17, and SCA27. Beam tests are sensitive to experimental therapies of various kinds including molecules affecting glutamate signaling, mesenchymal stem cells, anti-oligomer antibodies, lentiviral vectors carrying genes, interfering RNAs, or neurotrophic factors, and interbreeding with other mutants.
Cerebellum 2019 Jun
PMID:Motor Performances of Spontaneous and Genetically Modified Mutants with Cerebellar Atrophy. 3082 Aug 66

Oculomotor abnormalities are common in the spinocerebellar ataxias (SCAs). In studies of SCAs 1, 2, 3, and 6, eye movement abnormalities correlate with disease severity. Oculomotor abnormalities may be the sole motor manifestation of early and/or premanifest disease; however, not all ataxia rating scales include oculomotor assessment. We sought to identify the prevalence and characteristics of oculomotor abnormalities at first presentation in a large SCA cohort, including those in earlier stages of disease. We performed a retrospective assessment of initial clinical examinations of SCA patients followed in the Massachusetts General Hospital Ataxia Unit and assessed with the Brief Ataxia Rating Scale (BARS). One hundred thirty-four SCA patients were assessed: 17 SCA1, 13 SCA2, 55 SCA3, 2 SCA5, 22 SCA6, 11 SCA7, 9 SCA8, and 5 SCA17, mainly in the early stages of disease (67.2% stage 0-1). Oculomotor abnormalities were present on initial assessment in 94.8%, including 7/9 stage 0 and 77/81 stage 1 patients. Stage 0/1 patients had frequent saccadic intrusions, nystagmus, and hypo/hypermetric saccades. Saccadic slowing was present even in early stage SCA7 and SCA2, eventually leading to ophthalmoplegia. The burden of oculomotor abnormalities correlated with disease stage, duration, and severity, remaining highly significant even when controlling for age. The ubiquitous presence of oculomotor abnormalities in the SCAs, particularly early in the course, underscores the importance of oculomotor assessment in ataxia rating scales such as BARS. These findings highlight the potential for quantitative physiological oculomotor measures as clinical biomarkers in natural history studies and clinical trials.
Cerebellum 2019 Dec
PMID:Eye Movement Abnormalities Are Ubiquitous in the Spinocerebellar Ataxias. 3117 30

Essential tremor (ET) has recently been reconceptualized by many as a degenerative disease of the cerebellum. Until now, though, there has been no attempt to frame it within the context of these diseases. Here, we compare the clinical and postmortem features of ET with other cerebellar degenerations, thereby placing it within the broader context of these diseases. Action tremor is the hallmark feature of ET. Although often underreported in the spinocerebellar ataxias (SCAs), action tremors occur, and it is noteworthy that in SCA12 and 15, they are highly prevalent, often severe, and can be the earliest disease manifestation, resulting in an initial diagnosis of ET in many cases. Intention tremor, sometimes referred to as "cerebellar tremor," is a common feature of ET and many SCAs. Other features of cerebellar dysfunction, gait ataxia and eye motion abnormalities, are seen to a mild degree in ET and more markedly in SCAs. Several SCAs (e.g., SCA5, 6, 14, and 15), like ET, follow a milder and more protracted disease course. In ET, numerous postmortem changes have been localized to the cerebellum and are largely confined to the cerebellar cortex, preserving the cerebellar nuclei. Purkinje cell loss is modest. Similarly, in SCA3, 12, and 15, Purkinje cell loss is limited, and in SCA12 and 15, there is preservation of cerebellar nuclei and relative sparing of other central nervous system regions. Both clinically and pathologically, there are numerous similarities and intersection points between ET and other disorders of cerebellar degeneration.
Cerebellum 2020 Dec
PMID:Essential Tremor Within the Broader Context of Other Forms of Cerebellar Degeneration. 3266 85