Growth hormone deficiency type A due to a novel deletion in the hGH gene cluster

Abstract

A hGH gene deletion has been reported only in patients with type A complete GH deficiency. We had the opportunity to examine 12 children with isolated GH deficiency (10 boys and 2 girls) belonging to 6 families. In 10 cases (5 families) peak plasma GH after AITT varies between 0.9 and 7 ng/ml and were treated with some succes by hGH. Two boys (1 family) had autosomic recessive type A GH deficiency and produced high titer hGH antibodies shortly after onset of hGH administration that was unsuccessfull. DNA from the patients and family members was studied by restriction endonuclease analysis with a 32p labelled hGH cDNA probe. Analysis of the restriction pattern obtained in both parents and in the type A dwarfs showed the existence of an extensive deletion involving more than 40 kb of the GH gene cluster. The two children were homozygous for this deletion which left intact the hCS-L gene, removing on the 5′ side the hGH-N gene, and on the 3′ side the hCS-A, hGH-V and hCS-B sequences. No deletion was found in the other families.In conclusion, the present results are different from the deletions previously reported by Phillips et al, and further demonstrate the genomic heterogeneity of the familial isolated growth hormone deficiency type A.