Advertisement
Research Article Free access | 10.1172/JCI105833
Department of Medicine, Wayne State University, School of Medicine, Detroit, Michigan
Department of Pathology, Wayne State University, School of Medicine, Detroit, Michigan
Veterans Administration Hospital, Allen Park, Michigan
Detroit Institute for Cancer Research, and the Department of Human Genetics, (Simpson Memorial Institute), University of Michigan Medical School, Ann Arbor, Michigan 48207
Detroit Institute for Cancer Research, and the Department of Medicine (Simpson Memorial Institute), University of Michigan Medical School, Ann Arbor, Michigan 48207
Find articles by Prasad, A. in: JCI | PubMed | Google Scholar
Department of Medicine, Wayne State University, School of Medicine, Detroit, Michigan
Department of Pathology, Wayne State University, School of Medicine, Detroit, Michigan
Veterans Administration Hospital, Allen Park, Michigan
Detroit Institute for Cancer Research, and the Department of Human Genetics, (Simpson Memorial Institute), University of Michigan Medical School, Ann Arbor, Michigan 48207
Detroit Institute for Cancer Research, and the Department of Medicine (Simpson Memorial Institute), University of Michigan Medical School, Ann Arbor, Michigan 48207
Find articles by Tranchida, L. in: JCI | PubMed | Google Scholar
Department of Medicine, Wayne State University, School of Medicine, Detroit, Michigan
Department of Pathology, Wayne State University, School of Medicine, Detroit, Michigan
Veterans Administration Hospital, Allen Park, Michigan
Detroit Institute for Cancer Research, and the Department of Human Genetics, (Simpson Memorial Institute), University of Michigan Medical School, Ann Arbor, Michigan 48207
Detroit Institute for Cancer Research, and the Department of Medicine (Simpson Memorial Institute), University of Michigan Medical School, Ann Arbor, Michigan 48207
Find articles by Konno, E. in: JCI | PubMed | Google Scholar
Department of Medicine, Wayne State University, School of Medicine, Detroit, Michigan
Department of Pathology, Wayne State University, School of Medicine, Detroit, Michigan
Veterans Administration Hospital, Allen Park, Michigan
Detroit Institute for Cancer Research, and the Department of Human Genetics, (Simpson Memorial Institute), University of Michigan Medical School, Ann Arbor, Michigan 48207
Detroit Institute for Cancer Research, and the Department of Medicine (Simpson Memorial Institute), University of Michigan Medical School, Ann Arbor, Michigan 48207
Find articles by Berman, L. in: JCI | PubMed | Google Scholar
Department of Medicine, Wayne State University, School of Medicine, Detroit, Michigan
Department of Pathology, Wayne State University, School of Medicine, Detroit, Michigan
Veterans Administration Hospital, Allen Park, Michigan
Detroit Institute for Cancer Research, and the Department of Human Genetics, (Simpson Memorial Institute), University of Michigan Medical School, Ann Arbor, Michigan 48207
Detroit Institute for Cancer Research, and the Department of Medicine (Simpson Memorial Institute), University of Michigan Medical School, Ann Arbor, Michigan 48207
Find articles by Albert, S. in: JCI | PubMed | Google Scholar
Department of Medicine, Wayne State University, School of Medicine, Detroit, Michigan
Department of Pathology, Wayne State University, School of Medicine, Detroit, Michigan
Veterans Administration Hospital, Allen Park, Michigan
Detroit Institute for Cancer Research, and the Department of Human Genetics, (Simpson Memorial Institute), University of Michigan Medical School, Ann Arbor, Michigan 48207
Detroit Institute for Cancer Research, and the Department of Medicine (Simpson Memorial Institute), University of Michigan Medical School, Ann Arbor, Michigan 48207
Find articles by Sing, C. in: JCI | PubMed | Google Scholar
Department of Medicine, Wayne State University, School of Medicine, Detroit, Michigan
Department of Pathology, Wayne State University, School of Medicine, Detroit, Michigan
Veterans Administration Hospital, Allen Park, Michigan
Detroit Institute for Cancer Research, and the Department of Human Genetics, (Simpson Memorial Institute), University of Michigan Medical School, Ann Arbor, Michigan 48207
Detroit Institute for Cancer Research, and the Department of Medicine (Simpson Memorial Institute), University of Michigan Medical School, Ann Arbor, Michigan 48207
Find articles by Brewer, G. in: JCI | PubMed | Google Scholar
Published June 1, 1968 - More info
Detailed clinical and genetic studies have been performed in a Negro family, which segregated for sex-linked sideroblastic anemia and glucose-6-phosphate dehydrogenase (G-6-DP) deficiency. This is the first such pedigree reported. Males affected with sideroblastic anemia had growth retardation, hypochromic microcytic anemia, elevated serum iron, decreased unsaturated iron-binding capacity, increased 59Fe clearance, low 59Fe incorporation into erythrocytes, normal erythrocyte survival (51Cr), normal hemoglobin electrophoretic pattern, erythroblastic hyperplasia of marrow with increased iron, and marked increase in marrow sideroblasts, particularly ringed sideroblasts. Perinuclear deposition of ferric aggregates was demonstrated to be intramitochondrial by electron microscopy. Female carriers of the sideroblastic gene were normal but exhibited a dimorphic population of erythrocytes including normocytic and microcytic cells. The bone marrow studies in the female (mother) showed ringed marrow sideroblasts.
Studies of G-6-PD involved the methemoglobin elution test for G-6-PD activity of individual erythrocytes, quantitative G-6-PD assay, and electrophoresis. In the pedigree, linkage information was obtained from a doubly heterozygous woman, four of her sons, and five of her daughters. Three sons were doubly affected, and one was normal. One daughter appeared to be a recombinant. The genes appeared to be linked in the coupling phase in the mother. The maximum likelihood estimate of the recombination value was 0.14.
By means of Price-Jones curves, the microcytic red cells in peripheral blood were quantitated in female carriers. The sideroblast count in the bone marrow in the mother corresponded closely to the percentage of microcytic cells in peripheral blood. This is the second example in which the cellular expression of a sex-linked trait has been documented in the human red cells, the first one being G-6-PD deficiency. The coexistence of the two genes in doubly heterozygous females has made it possible to study correlations in cell counts; our studies showed a strong positive correlation except in the probable recombinant in which a reciprocal relation held which indicated that X-inactivation was at least regional, rather than locus by locus.
Images.