Studies of GH gene defects in familial Isolated Growth Hormone Deficiency (IGHD).

One family with isolated GH deficiency (IGHD) was Studied. To determine GHI gene deletions, PCR and Southern blot analyses were used. None of the possible deletions were found in the subjects but the GH1 gene mutation was found. The family consisted of parents (both 140 cm) and their three children with isolated GHD. The daughter and two sons were first seen between 2.9 and 5.3 years of age when their HtSDSs were -2.2 to -3.6, and peak GHs were 0.9 to 4.0 mg/ml. The GH1 gene change was found in G-->A substitution at +28 in the intervening sequence or intron 3 (IVS3+28 G-->A). This change is a dominant-negative mutation which has never occurred in any reports in any reports in Thailand and we were the first group to report here. The segregation which and expression studies of the IVS3+28 G-->A variant are underway to confirm whether it is a new dominant-negative mutation that causes GHD by perturbing mRNA splicing.

Molecular studies in growth hormone gene deletions in patients with isolated growth hormone deficiency.

Human GH deficiency (GHD) occurs in 1 in 4,000-10,000, and up to 30 percent of cases have an affected first degree relative suggesting many cases may be familial. To determine the GHD cases cased by GH gene defects we analyzed the GH genes of 90 consecutive cases. Genomic DNAs were used for PCR amplification of 2.7 kb fragments containing subjects’ GH gene; these PCR products were subjects to determine GH gene deletions. PCR products of 1900 and 1919 bp were obtained. By using the combination of restriction enzymes BglI, HaeII and SmaI to digest these PCR products, the various sizes of GH gene deletion can be detected. None of the possible deletions was found in these patients by either PCR or Southern blot analysis.