Abstract 4

To determine the type and frequency of GH gene deletions in Brazilians with severe isolated GH deficiency we screened DNAs from 23 patients (12 males, 11 females: heights -4.9 ± 1.4 SDS). Genomic DNA was screened for GH gene deletions by restriction endonuclease analysis of polymerase chain reaction amplification products. Deletions of the GH gene (two 6.7 kb and one 7.6 kb) were found in three unrelated patients with typical features of severe GH deficiency. The two patients with 6.7 kb deletions developed growth-attenuating anti-GH antibodies whereas the patient with a 7.6 kb deletion continues to grow with after 2 years of GH replacement therapy. Our finding that 3/23 ( 13%) of Brazilian subjects had GH gene deletions agrees with previous studies of severe isolated GH deficiency subjects in other populations and 2/3 ( 67%) of subjects with deletions developed blocking antibodies despite administration of exogenous GH in low doses. Interestingly, only 1/10 of cases with affected relatives or parental consanguinity had GH-1 gene deletions, suggesting that smaller deletions or point mutations in exons, introns or promoter region of the GH gene might be involved in these patients. (FAPESP 1996/1738-6 and 1996/12354-4).