An effect of gene dosage on production of human chorionic somatomammotropin.

The gene deletions responsible for isolated partial deficiency of fetal human chorionic somatomammotropin (hCS) production were characterized by restriction endonuclease analysis of genomic DNA prepared from the leukocytes of an affected child. The phenotypically normal child was the product of a 38-week pregnancy characterized by peak maternal hCS levels of 1.1 micrograms/microliter (normal, 3-9.2 micrograms/ml) and normal levels of other pregnancy-associated hormones. Two genes, termed hCS-A and hCS-B, specify the same mature hCS peptide and are responsible for fetal hCS production. Digestion of the child's DNA with the enzymes Hind III, Eco RI, Bam HI, Bgl II, Hinc II and Msp I disclosed absence of the restriction fragments that normally contain the hCS-A gene. However, the hCS-B gene was present in the child's DNA. The child's DNA digests contained an abnormally large Eco RI fragment of 10.0 kb containing the hCS-L gene. This abnormal fragment is a marker for a deletion that is responsible for complete deficiency of hCS when present in the homozygous state. The child's DNA restriction patterns were consistent with heterozygosity for two different deletions involving hCS genes. The paternal hGH gene cluster lacked the hCS-A, human GH variant, and hCS-B genes, while the maternal cluster lacked only the hCS-A gene. Thus, the child's DNA contained only one of the normal complement of four functional hCS genes per diploid genome. Material hCS levels approximately one fourth as great as those present at comparable stages of normal pregnancies indicated that there was no compensatory increase in expression of the remaining hCS gene.