Abstract | BACKGROUND: METHODS: RESULTS:
DNA-sequencing studies in two affected males and one carrier female in the kindred demonstrated a cytosine-to- guanine change at nucleotide 1215 (in exon 8). This change results in the substitution of serine for threonine at amino acid residue 388, near the lysine that binds the pyridoxal phosphate cofactor. In expression studies, the activity of the mutant enzyme was reduced relative to that of the wild type, and this reduction was comparable to that in erythroid cells of the proband during relapse of the anemia; the enzyme activity expressed in the presence of pyridoxine was comparable to that in the proband's marrow cells during remission. Although the affinity of the mutant enzyme for pyridoxal phosphate was not altered, the mutation appears to introduce a conformational change at the active site of the enzyme. CONCLUSIONS:
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Authors | T C Cox, S S Bottomley, J S Wiley, M J Bawden, C S Matthews, B K May |
Journal | The New England journal of medicine
(N Engl J Med)
Vol. 330
Issue 10
Pg. 675-9
(Mar 10 1994)
ISSN: 0028-4793 [Print] United States |
PMID | 8107717
(Publication Type: Case Reports, Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- DNA, Complementary
- Isoenzymes
- 5-Aminolevulinate Synthetase
- Pyridoxine
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Topics |
- 5-Aminolevulinate Synthetase
(genetics)
- Aged
- Amino Acid Sequence
- Anemia, Sideroblastic
(drug therapy, enzymology, genetics)
- Base Sequence
- DNA, Complementary
- Erythroblasts
(enzymology)
- Female
- Genetic Linkage
- Humans
- Isoenzymes
(genetics)
- Male
- Molecular Sequence Data
- Pedigree
- Point Mutation
- Pyridoxine
(therapeutic use)
- X Chromosome
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