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)

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) was originally found among inhabitants of the Charlevoix-Saguenay region of northeastern Quebec in Canada. This disease is a neurodegenerative disorder characterized by early-onset spastic ataxia, dysarthria, nystagmus, distal muscle wasting, finger and foot deformities, and retinal hypermyelination. The principal neuropathology comprises atrophy of the upper vermis and the loss of Purkinje cells in the cerebellum. The SACS gene was originally reported to consist of a single gigantic exon spanning 12.8 kb with an 11.5-kb open reading frame (ORF), and to encode the protein sacsin. Recently, eight exons upstream from the original gigantic one, however, have been found, and the new ORF has elongated to 13.7 kb. To date, at least 28 mutations have been found in Quebec and non-Quebec patients including ones in Italy, Japan, Spain, Tunisia, and Turkey, and ARSACS thus shows a worldwide occurrence. Although most of the mutations reported have been in the gigantic exon, the genotype is now expanding upstream from this gigantic exon. Therefore, the new exons upstream of the gigantic one should be analyzed when a case is clinically compatible with ARSACS, even without any mutation in the gigantic exon. Although Quebec patients show a homogeneous phenotype, non-Quebec patients exhibit some atypical clinical features, as follows: slightly later onset than that in Quebec patients, absence of retinal hypermyelination, intellectual impairment, and lack of spasticity. Thus, since ARSACS shows the clinical diversity, the SACS gene should be analyzed not only in typical cases as Quebec patients but also in atypical cases as non-Quebec patients. As more SACS mutations are identified worldwide, the clinical spectrum of 'sacsinopathies' will expand, and a finer genotype-phenotype correlation study will become possible and shed light on the molecular mechanism underlying ARSACS.
Cerebellum 2007
PMID:Sacsinopathies: sacsin-related ataxia. 1785 17

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is characterized by the presence of myelinated retinal fibers. This typical feature is very helpful for the diagnosis but is not always observed in patients outside Quebec. Apart from phenotype variations, misinterpretation of the funduscopy may explain discrepancies and misdiagnosis. We analyze the modification of retinal fibers layer using the funduscopy and the optical coherence tomography (OCT) in two French patients having spinocerebellar ataxia associated with a spastic paraparesia with genetically confirmed ARSACS. In both patients the funduscopy showed a swollen and striated aspect of peripapillar fibers along the retinal vessels and in the intermaculopapillar region. The OCT displayed an important thickening of the optical fibers layer mainly in upper and lower temporal area without attenuation of deep layers, as well as a filling in of the foveolar depression with thickening of the ganglion cell layer normally absent from the foveola. The aspect of funduscopy and OCT in our patients does not correspond to the classical description of myelin fibers encountered in 0.3% to 1% of the population. Thus, ARSACS might be underdiagnosed because of an erroneous interpretation of funduscopy. When considering the diagnosis of ARSACS, the neurologist should ask the ophthalmologist to search for thickening of peripapillar retinal fibers by both funduscopy and OCT rather than myelinated retinal fibers. This ophthalmological consideration has avoided misdiagnosis and led to the description of new mutations in our cases.
Cerebellum 2011 Dec
PMID:Thickening of peripapillar retinal fibers for the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay. 2159 85

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare neurodegenerative disorder characterized by the triad of early-onset cerebellar ataxia, peripheral sensorimotor neuropathy, and lower limb spasticity. Here, we present a 28-year-old male patient with symptoms of ARSACS and mild intellectual disability from a consanguineous family of tribal J&K, India. Whole exome sequencing unraveled a novel homozygous frameshift SACS mutation (Cys2869ValfsTer15) in the patient. In addition to the well-established ARSACS imaging features, MRI revealed T2 hyperintense rim around the thalami ("bithalamic stripes") demonstrating that this feature might serve as an additional supportive diagnostic imaging marker for ARSACS. Moreover, retinal nerve fiber layer thickening which has recently been proposed as a diagnostic biomarker for ARSACS was present on routine optic coherence tomography (OCT) also in this patient, indicating that it might indeed present a relatively universal diagnostic biomarker for ARSACS. In sum, our findings extend the geographical distribution of ARSACS to even very remote tribal regions in Asia (such as the Rajouri region of J&K, India) and extend the mutational and imaging spectrum of ARSACS. They provide further support that brain imaging and OCT markers might serve as diagnostic biomarkers for ARSACS in patients with novel SACS mutations, applicable even in remote regions of the world to identify and confirm ARSACS disease.
Cerebellum 2019 Aug
PMID:ARSACS as a Worldwide Disease: Novel SACS Mutations Identified in a Consanguineous Family from the Remote Tribal Jammu and Kashmir Region in India. 3096 95