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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of genome wide genotyping arrays has the potential to assess entire groups of genetic disorders in one application and has begun to emerge as an aid to diagnosis in clinical practice. Recessive families may suffer from diseases because of homozygosity of recessive alleles; homozygosity tracks can be easily identified by using these high throughput SNPs arrays, allowing the rapid mapping of autozygous segments that may be associated with the disease. According to this, we performed homozygosity mapping using genome wide SNP arrays in a North Indian family with an autosomal recessive disorder of ataxia, epilepsy, cognitive decline and visual problems. In this kindred, a large number of homozygous regions were identified. In silico analysis was also carried out. The COL18A1 gene found in one of the homozygous tracks has genetic defects previously reported with a similar phenotype as our family. Hence, it was the most likely candidate gene and at large the first to be analyzed. A homozygous COL18A1 two base pair deletio segregating with the disease was identified; expanding the spectrum of disease seen in COL18A1 and proving that the genetic lesion underlying recessive disorders can rapidly identify by employing genotyping arrays along with detailed candidate gene analysis.
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PMID:Homozygosity mapping through whole genome analysis identifies a COL18A1 mutation in an Indian family presenting with an autosomal recessive neurological disorder. 1916 Apr 45

The Spt-Ada-Gcn5 Acetyltransferase (SAGA) complex is a transcriptional coactivator with histone acetylase and deubiquitinase activities that plays an important role in visual development and function. In Drosophila melanogaster, four SAGA subunits are required for the deubiquitination of monoubiquitinated histone H2B (ubH2B): Nonstop, Sgf11, E(y)2, and Ataxin 7. Mutations that disrupt SAGA deubiquitinase activity cause defects in neuronal connectivity in the developing Drosophila visual system. In addition, mutations in SAGA result in the human progressive visual disorder spinocerebellar ataxia type 7 (SCA7). Glial cells play a crucial role in both the neuronal connectivity defect in nonstop and sgf11 flies, and in the retinal degeneration observed in SCA7 patients. Thus, we sought to identify the gene targets of SAGA deubiquitinase activity in glia in the Drosophila larval central nervous system. To do this, we enriched glia from wild-type, nonstop, and sgf11 larval optic lobes using affinity-purification of KASH-GFP tagged nuclei, and then examined each transcriptome using RNA-seq. Our analysis showed that SAGA deubiquitinase activity is required for proper expression of 16% of actively transcribed genes in glia, especially genes involved in proteasome function, protein folding and axon guidance. We further show that the SAGA deubiquitinase-activated gene Multiplexin (Mp) is required in glia for proper photoreceptor axon targeting. Mutations in the human ortholog of Mp, COL18A1, have been identified in a family with a SCA7-like progressive visual disorder, suggesting that defects in the expression of this gene in SCA7 patients could play a role in the retinal degeneration that is unique to this ataxia.
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PMID:Transcriptome Profiling Identifies Multiplexin as a Target of SAGA Deubiquitinase Activity in Glia Required for Precise Axon Guidance During Drosophila Visual Development. 2726 Oct 2