Short stature in carriers of recessive mutation causing familial isolated growth hormone deficiency Academic Article uri icon


  • Isolated growth hormone deficiency (IGHD) IB is an autosomal recessive disorder characterized by a good response to exogenous growth hormone (GH) treatment without development of anti‐GH antibodies. Patients with IGHD IB were found to be compound heterozygotes for deletion and frameshift mutations as well as homozygotes for splicing mutations in the GH‐1 gene. Recently, a novel splicing mutation in the GH‐1 gene was identified in an extended, consanguineous Arab‐Bedouin family from Israel with IGHD IB. Prior to the identification of this mutation, a considerable number of children with short stature in this family were found normal on pharmacological stimulation for GH release. This observation prompted a genotype/phenotype correlation of potential heterozygotes in the family. Carriers of the mutant GH‐1 allele were found as a group to have a significantly shorter stature than normal homozygote (mean standard deviation scores, 1.67 and −0.40, respectively, P < 0.05). Moreover, 11 of 33 (33%) heterozygotes, but only 1 of 17 (5.9%) normal homozygotes, had their height at 2 or more SD below the mean. Overall, 48.5% of studied heterozygotes were found to be of appreciably short stature with height at or lower than the 5th centile (≥ −1.7 SD), whereas only 5.9% of the normal homozygotes did (P < 0.004). This phenomenon of heterozygotes for a recessive mutation in the GH‐1 gene manifesting short stature, might imply that some such mutations may account for non‐GH deficiency reduced height in the general population. Am. J. Med. Genet. 90:188–192, 2000. © 2000 Wiley‐Liss, Inc.

publication date

  • January 1, 2000