Short stature in carriers of recessive mutation causing familial isolated growth hormone deficiency

Esther Leiberman, Dorit Pesler, Ruti Parvari, Khalil Elbedour, Hussein Abdul-Latif, Milton R. Brown, John S. Parks, Rivka Carmi

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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.

Original languageEnglish
Pages (from-to)188-192
Number of pages5
JournalAmerican Journal of Medical Genetics
Issue number3
StatePublished - 31 Jan 2000


  • GH-1
  • Heterozygotes
  • Recessive inheritance
  • Short stature
  • Splicing mutation

ASJC Scopus subject areas

  • Genetics(clinical)


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