Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The newly recognized ataxia-ocular apraxia 1 (AOA1; MIM 208920) is the most frequent cause of autosomal recessive ataxia in Japan and is second only to Friedreich ataxia in Portugal. It shares several neurological features with ataxia-telangiectasia, including early onset ataxia, oculomotor apraxia and cerebellar atrophy, but does not share its extraneurological features (immune deficiency, chromosomal instability and hypersensitivity to X-rays). AOA1 is also characterized by axonal motor neuropathy and the later decrease of serum albumin levels and elevation of total cholesterol. We have identified the gene causing AOA1 and the major Portuguese and Japanese mutations. This gene encodes a new, ubiquitously expressed protein that we named aprataxin. This protein is composed of three domains that share distant homology with the amino-terminal domain of polynucleotide kinase 3'- phosphatase (PNKP), with histidine-triad (HIT) proteins and with DNA-binding C2H2 zinc-finger proteins, respectively. PNKP is involved in DNA single-strand break repair (SSBR) following exposure to ionizing radiation and reactive oxygen species. Fragile-HIT proteins (FHIT) cleave diadenosine tetraphosphate, which is potentially produced during activation of the SSBR complex. The results suggest that aprataxin is a nuclear protein with a role in DNA repair reminiscent of the function of the protein defective in ataxia-telangiectasia, but that would cause a phenotype restricted to neurological signs when mutant.
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PMID:The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin. 1158

Growth Factor Independence 1 (Gfi1) is a transcriptional repressor with a molecular weight between 47 and 55 kDa The protein has six C-terminal C2H2-type zinc-finger domains and a characteristic stretch of 20 amino acids, called the SNAG-domain, at its N-terminus. Expression of Gfi1 ranges from the hematopoietic and lymphoid system, to sensory epithelia, lung and parts of the CNS. Gene knock-out studies revealed that Gfi1 is essential for the development of granulocytes and plays a role in T-cell differentiation and macrophage-dependent cytokine production, indicating that this protein shares responsibility for different lines of defense against pathogens. Also, Gfi1 is required for the proper development of inner ear hair cells illustrated by ataxia and deafness in knock-out mice. While hereditary hearing loss has so far not been associated with Gfi1 malfunction, crippling mutations in the Gfi1 gene have been reported in patients suffering from neutropenia suggesting an important role of Gfi1 in this human disease.
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PMID:The zinc finger transcription factor Growth factor independence 1 (Gfi1). 1561 11