Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fanconi anemia (FA) is an autosomal recessive disease characterized by congenital anomalies, aplastic anemia, and chromosomal instability. A cDNA encoding the FA complementation group C (FACC) polypeptide was recently cloned [Strathdee, C. A., Gavish, H., Shannon, W. R. & Buchwald, M. (1992) Nature (London) 356, 763-767]. To further characterize this polypeptide, we generated a rabbit polyclonal antiserum against its carboxyl terminus. We used this antiserum to analyze the FACC polypeptide from normal or mutant (FA) lymphoblast cell lines. By immunoprecipitation, the wild-type FACC was a 60-kDa protein, consistent with its predicted molecular mass. FA group C cell lines expressed full-length FACC, truncated FACC, or no detectable FACC polypeptide. In addition, the antiserum specifically immunoprecipitated a 50-kDa and a 150-kDa FACC-related protein (FRP-50 and FRP-150). Unexpectedly, cell fractionation and immunofluorescence studies demonstrated that the FACC polypeptide localizes to the cytoplasm. In conclusion, we have generated an antiserum specific for the human FACC polypeptide. The antiserum should be useful for screening FA cells for mutant FACC polypeptides and for identifying and cloning FACC-related proteins.
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PMID:The Fanconi anemia polypeptide FACC is localized to the cytoplasm. 751 62

Fanconi anemia (FA) is an autosomal recessive disease characterized by congenital anomalies, aplastic anemia, and cancer susceptibility. Mutations within the FA complementation group C (FAC) gene account for approximately 14% of diagnosed FA cases. Two mutations, one in exon 1 (delG322) and one in exon 4 (IVS4 + 4 A to T), account for 90% of known FAC mutations. The delG322 mutation results in a mild FA phenotype, while the IVS4 + 4 A to T mutation results in severe FA phenotype. To determine the molecular basis for this clinical variability, we analyzed patient-derived cell lines for the expression of characteristic mutant FAC polypeptides. All cell lines with the delG322 mutation expressed a 50-kD FAC polypeptides, FRP-50 (FAC-related protein), shown to be an amino terminal truncated isoform of FAC reinitiated at methionine 55. All cell lines with the IVS4 + 4 A to T mutation lacked FRP-50. Overexpression of a cDNA encoding FRP-50 in an FA(C) cell line resulted in partial correction of mitomycin C sensitivity. In conclusion, expression of an amino terminal truncated FAC protein accounts, at least in part, for the clinical heterogeneity among FA(C) patients.
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PMID:Clinical variability of Fanconi anemia (type C) results from expression of an amino terminal truncated Fanconi anemia complementation group C polypeptide with partial activity. 863 4