The serum growth hormone (GH) response to provocative tests is dependent on type of assay in autosomal dominant isolated GH deficiency (IGHD) due to an ARG183 HIS (R183H) GH-I gene mutation.

MARINO R,; CHALER E,; WARMAN M,; CIACCIO M,; BERENSZTEIN E,; RIVAROLA MA,; BELGOROSKY, A

Clinical Chemistry

Amer Assoc for Clin Chemistry

Lugar: Stanford; Año: 2003 vol. 49 p. 1002 - 1005

1530-8561

The clinical appearance and genetic basis of familial isolated growth hormone deficiency (IGHD) are heterogeneous and are associated with at least four types of Mendelian disorders: two forms with autosomal recessive inheritance (IGHD type 1A and 1B), one with autosomal dominant inheritance (IGHD type 2), and one with Xlinked inheritance (IGHD type 3). Our study showed that affected members of the two families carry the R183H point mutation in exon 5. We also detected two additional point mutations at positions 52 and 56 of intron 1. This novel finding suggests that genotype and phenotype variations exist among different families. These intronic mutations could represent normal polymorphism variants, or they might determine alternativesplicing, generating GH isoforms that could contribute to changes in the ratio between 22-kDa GH and non-22-kDa GH. to provocative stimuli depends on the assay selected to measure serum GH and suggests that altered circulating GH isoforms may be important in defining the GHD phenotype in these patients. GH isoforms might have a reversible dominant-negative effect at the GHR level. Impaired GH secretion may present also, as suggested by the absence of GH hypersecretion. Interestingly, the dominant-negative effects were overcome by administration ofrhGH at a dose similar to that used to treat nonfamilial GHD