Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016719 (Friedreich's ataxia)
 2,098 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report an autosomal recessive form of ataxia that is not allelic to Friedreich's disease in six individuals from a large kindred with family origins traced to a common founder of German-Swiss descent. The disorder begins during early childhood with a concentric contraction of the visual fields and proprioceptive loss. Eventually blindness, a severe sensory ataxia, achalasia, scoliosis, and inanition develop by third decade. Inversion recovery MRIs of the spinal cord in affected individuals demonstrate a hyperintense signal in the posterior columns. Finding the gene responsible for this disorder may aid in our understanding of the mechanisms that cause sensory neuronal degeneration.
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PMID:An autosomal recessive disorder with posterior column ataxia and retinitis pigmentosa. 985 54

There has been a recent explosion in knowledge regarding the genetic basis of several autosomal recessive ataxias. This article summarizes current information regarding rare forms of recessive ataxias. Friedreich's ataxia and ataxia telangiectasia are dealt with in other articles in this issue. The rarer recessive ataxias can be clinically classified as sensory and spinocerbellar ataxias, cerebellar ataxia with sensory-motor polyneuropathy, and purely cerebellar ataxias. Examples of the first category include ataxia with isolated vitamin E deficiency, abetalipoproteinemia, Refsum's disease, infantile-onset spinocerebellar ataxia, and ataxia with blindness and deafness. Examples of ataxia with sensory-motor polyneuropathy include ataxia with oculomotor apraxia 1 and 2 and spinocerebellar ataxia with neuropathy 1. Examples of purely cerebellar ataxia include autosomal recessive spastic ataxia of Charlevoix-Saguenay and ataxia with hypogonadotropic hypogonadism. This review summarizes the clinical and genetic features of these entities and concludes that the pathogenic basis of such ataxias at this time appear to involve two broad types of processes: free-radical injury and defects of DNA single- or double-strand break repair.
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PMID:Rare forms of autosomal recessive neurodegenerative ataxia. 1465 6

Friedreich ataxia (FRDA) is typically characterized by slowly progressive ataxia, depressed tendon reflexes, dysarthria, pyramidal signs, and loss of position and vibration sense with onset before 25 years. While several atypical forms of FRDA are recognized, profound vision deficit is rare. We describe here a 41-year-old man with profound vision deficit and episodic complete blindness associated with marked optic atrophy, spastic paraparesis, and sensory neuropathy without ataxia whose diagnostic evaluation revealed compound heterozygosity for two frataxin mutations, a 994 GAA repeat intronic expansion and c.389G > T (p.G130V) missense mutation. This case emphasizes that FRDA should be considered for individuals with significant vision deficit with optic atrophy and sensory neuropathy, even in the absence of ataxia. This case also raises the additional, related concern that prior studies may underestimate the frequency and varieties of variant forms of FRDA.
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PMID:Atypical, perhaps under-recognized? An unusual phenotype of Friedreich ataxia. 2016 37

Leber congenital amaurosis (LCA), a form of autosomal recessive severe early-onset retinal degeneration, is an important cause of childhood blindness. This may be associated with systemic features or not. Here we identified COG5 compound-heterozygous variants in patients affected with a complex LCA phenotype associated with microcephaly and skeletal dysplasia. COG5 is a component of the COG complex, which facilitates retrograde Golgi trafficking; if disrupted this can result in protein misfolding. To date, variants in COG5 have been associated with a distinct congenital disorder of glycosylation (type IIi) and with a variant of Friedreich's ataxia. We show that COG5 variants can also result in fragmentation of the Golgi apparatus and upregulation of the UPR modulator, PKR-like endoplasmic reticulum kinase (PERK). In addition, upregulation of PERK induces DNA damage in cultured cells and in murine retina. This study identifies a novel role for COG5 in maintaining ER protein homeostasis and that disruption of that role results in activation of PERK and early-onset retinal degeneration, microcephaly and skeletal dysplasia. These results also highlight the importance of the UPR pathway in early-onset retinal dystrophy and as potential therapeutic targets for patients.
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PMID:COG5 variants lead to complex early onset retinal degeneration, upregulation of PERK and DNA damage. 3327 29