The Inheritance of the Sickling Phenomenon, with Particular Reference to Sickle Cell Disease

Abstract

Abstract 1. The manner of inheritance of the sickling phenomenon has been investigated in 75 kindreds, with hematologic observations on 465 persons. 2. Data are presented to support the contention that with a possible rare exception, the differential diagnosis between the sickle cell trait and sickle cell anemia is readily made. 3. The hematologic findings pertinent to a decision as to the mode of heredity of the sickle cell trait and sickle cell disease are as follows: a. Out of a total of 94 parents of children with sickle cell disease, 93 have shown the sickle cell trait. b. The incidence of sickle cell disease in segregating sibships would appear to lie between 0.18 and 0.26. c. In sibships segregating for sickle cell disease, the ratio of sickle cell trait to normal is approximately 2:1, but in sibships resulting from the marriage of a normal person with an individual with the sickle cell trait, the ratio of sickle cell trait to normal is significantly less than 1:1. d. Of the 4 children in this series who have a parent with sickle cell disease, all have the sickle cell trait. 4. The most reasonable hypothesis which will render the above data intelligible is that the sickling phenomenon is due to a gene which in single dose (heterozygous condition) produces only the sickle cell trait, and in double dose (homozygous condition), sickle cell disease. The chief and only discrepancy between theory and fact at the present time appears to lie in a deficiency of individuals with the sickle cell trait in certain types of matings. 5. No clear cut differences between normal and sickle cell trait were observed with respect to erythrocyte number, hemoglobin level, hematocrit, the cell constants, the leukocyte number or the differential count. 6. Certain minor hematologic abnormalities encountered in the kindreds under study and not obviously related to the sickling phenomenon are described.