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)

A 25-year-old male with a history of recurrent infections presented with fever, severe aplastic anaemia, splenomegaly and retroperitoneal node enlargement. Lympho-histiocytic granulomas were found in spleen, liver and lymph nodes. Granulocyte studies revealed normal morphology, severely impaired random migration and complete absence of directed locomotion. Whereas phagocytosis was slightly reduced, candidacidal activity and nitroblue tetrazolium reduction were normal. Basal granulocyte cyclic GMP levels were within the normal range while a 5-fold increase of cyclic AMP levels was observed. Numerous abnormalities were also found in the patient's lymphocytes: lack of delayed hypersensitivity, reduced response to mitogens, low OKT4/OKT8 ratio, absence of natural killer (NK) activity with normal number of cells recognized by NK-specific monoclonal antibodies. These observations describe a distinct clinico-pathologic entity and suggest the possibility of a common defect in granulocytes and in NK cells.
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PMID:Defective granulocyte chemotaxis and natural killer activity in a patient with recurrent infections. 302 45

Fanconi anemia is a rare disease characterized by congenital malformations, aplastic anemia, and predisposition to cancer. Despite the consolidated role of the Fanconi anemia proteins in DNA repair, their involvement in mitochondrial function is emerging. The purpose of this work was to assess whether the mitochondrial phenotype, independent of genomic integrity, could correlate with patient phenotype. We evaluated mitochondrial and clinical features of 11 affected individuals homozygous or compound heterozygous for p.His913Pro and p.Arg951Gln/Trp, the two residues of FANCA that are more frequently affected in our cohort of patients. Although p.His913Pro and p.Arg951Gln proteins are stably expressed in cytoplasm, they are unable to migrate in the nucleus, preventing cells from repairing DNA. In these cells, the electron transfer between respiring complex I-III is reduced and the ATP/AMP ratio is impaired with defective ATP production and AMP accumulation. These activities are intermediate between those observed in wild-type and FANCA-/- cells, suggesting that the variants at residues His913 and Arg951 are hypomorphic mutations. Consistent with these findings, the clinical phenotype of most of the patients carrying these mutations is mild. These data further support the recent finding that the Fanconi anemia proteins play a role in mitochondria, and open up possibilities for genotype/phenotype studies based on novel mitochondrial criteria.
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PMID:Hypomorphic FANCA mutations correlate with mild mitochondrial and clinical phenotype in Fanconi anemia. 2926 25