Confirming the laboratory-derived data, a heterozygous splice enhancer mutation in exon 3 (exon 3 + 2 A-->C) coding for GH-E32A mutation of the GH-1 gene was found in two independent pedigrees, causing familial IGHD II.
A single amino acid substitution in the exoplasmic domain of the human growth hormone (GH) receptor confers familialGH resistance (Laron syndrome) with positive GH-binding activity by abolishing receptor homodimerization.
At least three different sizes of GH-1 gene deletions (approximately 6.7, 7.0 and 7.6 kilobases) have been detected by Southern blot analysis of DNA from individuals with familial isolated GH deficiency type IA (IGHD1A).
Impaired thyrotropin responses to thyrotropin-releasing hormone distinguish these patients from most cases of idiopathic or familial deficiency of thyrotropin and growth hormone.