Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autosomal Recessive Cerebellar Ataxia type 1 (ARCA1), also known as recessive ataxia of Beauce, is an adult onset pure cerebellar ataxia that typically presents with cerebellar ataxia and/or dysarthria. A mutation in the synaptic nuclear envelope protein 1 (SYNE1) gene that is located on chromosome 6p25 results in premature termination of the protein. It was first reported in 2007 as the first identified gene responsible for a recessively inherited pure cerebellar ataxia. In this article, we are presenting two brothers with ARCA1 who were misdiagnosed and treated as multiple sclerosis for more than a decade. We are not only presenting a rare mutation in a Saudi family, but we are also expanding on the heterogeneity of the clinical presentation of this disorder and elaborating on the pathophysiology of neurological involvement. These cases illustrate that white matter abnormalities on MRI may occur in ARCA1. The clinical and radiological spectrum of ARCA1 indicate that this disease is more than a pure cerebellar degeneration. ARCA1 should be considered in the differential diagnosis of patients diagnosed with MS especially in the presence of strong family history. The disease is gradually progressive, and clinical features are atypical for MS. Applying diagnostic criteria for MS is extremely important for confirming or excluding the diagnosis. Detailed history and physical examination are of paramount importance to score the final diagnosis. Another less likely possibility is a chance association, which may question the biological relevance of our data. To confirm or exclude this possibility, further studies reporting different cohorts need to be conducted.
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PMID:Autosomal Recessive Cerebellar Ataxia type 1 mimicking multiple sclerosis: A report of two siblings with a novel mutation in SYNE1 gene in a Saudi family. 2801 57

The spectrin repeat-containing nuclear envelope protein 1 (SYNE1) gene encodes a family of spectrin structural proteins that are associated with anchoring the plasma membrane to the actin cytoskeleton. SYNE1-related disease is most commonly reported in autosomal recessive spinocerebellar ataxia 8, which demonstrates variable age of onset with a median of 30 years of age. However pathogenic mutations in SYNE1 are also causative of arthrogryposis multiplex congenital, a severe congenital neuromuscular condition. Here in we report monozygous twins with childhood onset ataxia, cerebellar hypoplasia, dysarthria, and cognitive impairment sharing two novel heterozygous mutations in the SYNE1 gene. Our family may expand the clinical phenotype associated with SYNE1-related disease and offers possible genotype-phenotype correlations of a rare continuum of clinical disease phenotypes from neonatal to adult onset.
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PMID:SYNE1-related autosomal recessive cerebellar ataxia, congenital cerebellar hypoplasia, and cognitive impairment. 3027 42