Quantitative abnormalities of allotypic genes in families with primary immune deficiencies.

Genetic antigens of human immunoglobulin G (Gm factors) were measured in members of the families of selected patients with primary immunodeficiency. The sera of seven out of 27 heterozygous relatives had either deficient concentrations of one Gm allotype or an unbalanced ratio of Gm(f)/Gm(a). Since these markers for allelic IgG1 genes are found in almost equal amounts in normal heterozygous persons, the results suggested that there was a quantitative deficiency in the expression in serum of one Gm gene. In several families allotype abnormalities were found in three successive generations; in one instance the quantitative defect appeared to segregate independently of the Gm genes. The experimental data failed to support a recessive gene hypothesis, in that too few of the close relatives had evidence indicating that they were carriers of defective Gm genes. The results were interpreted as consistent with an inherited regulatory defect in certain families with this disorder.