Isolated growth hormone (GH) deficiency type 1A associated with a double deletion in the human GH gene cluster.

The gene deletions responsible for isolated GH deficiency type 1A were characterized by direct analysis of genomic DNA prepared from the leukocytes of two affected children. The probands had typical symptoms of severe isolated GH deficiency complicated by antibody development and growth arrest after human (h) GH treatment. DNA analysis using the restriction endonucleases Eco RI, Bam HI, and Hind III revealed that the restriction fragment containing the hGH-N gene was absent along with those bearing the human chorionic somatomammotropin (hCS)-A and -B and hGH-V sequences. A total of about 40 kilobases DNA were absent due to two separate deletions flanking the hCS-L gene. The two affected siblings are homozygous for this rearrangement of the hGH/hCS gene cluster, which could have been generated by homologous crossing over between two different chromosomes, one bearing one of the previously described deletions of the hGH-N gene, and one bearing a deletion of DNA containing the hCS-A, hCS-B, and hGH-V sequences. Alternatively, this abnormality could have been generated by a complex intrachromosomal rearrangement. The parents, who are consanguinous, have DNA restriction patterns consistent with heterozygosity for this double deletion. This type of deletional mutation is the first involving multiple deletion of the hGH and hCS gene cluster.