Two cases of sickle cell disease presumably due to the combination of the genes for thalassemia and sickle cell hemoglobin.

By JAMES V. NEEL, PH.D., M.D., HARVEY A. ITANO, PH.D., M.D., AND JOHN S. LAWRENCE, M.D. I N RECENT YEARS our knowledge of the etiology of sickle cell disease has increased considerably. As a rule, both parents of a child with this disease show the sickle cell trait. This has led to the hypothesis that usually sickle cell disease is due to homozygosity for a gene which, when heterozygous, results only in the sickle cell trait . ‘ Occasionally, however, families are encountered in which the blood of oniy one of the parents of a child with clinical sickle cell disease can be induced to sickle. The study of such families has thus far resulted in the recognition of 3 other genetic types of sickle cell disease. In each of these 3 other types, the nonsickling parent is heterozygous for a gene responsible for another hematologic abnormality. The children who develop sickle cell disease in these families receive the gene responsible for the sickling phenomenon from one parent and 1 of the 3 other genes mentioned above from the other parent. The 3 other genes in question are: 1) the gene responsible for thalassemia, 6 2) the gene responsible for hemoglobin-c (hemoglobin-III),78 and 3) the gene responsible for hemoglobin-d.9 By now, approximately 18 families have been described in Italy, South America, and the United States in which sickle cell disease was presumably due to the first of the 3 less common mechanisms mentioned above, i.e., heterozygosity for both the sickle cell and the thalassemia genes.56’ ‘#{176}“ It is the purpose of the present report to describe still another such family. The justification for so doing is that the bloods of the 2 presumed “double heterozygotes” in this family have been subjected both to electrophoretic and alkaline denaturation studies, with results of some theoretic interest.