Mutations in the growth hormone releasing hormone receptor: a new form of dwarfism in humans.

Abstract

We describe a recently identified new form of dwarfism due to isolated growth hormone (GH) deficiency, secondary to inactivating mutations in the GH-releasing hormone receptor (GHRHR) gene. The identical nonsense mutations in the extracellular domain of the GHRHR (E72X or E50X, depending on whether the signal peptide is included in the numbering) has been independently described in three families residing on or originating from the Indian subcontinent (Pakistan, the Bombay region, and Delft near Sri Lanka). Another inactivating mutation, involving the donor splice site of intron 1, has been identified in a population in north-eastern Brazil. Genetic transmission is autosomal recessive; the gene is located on the short arm of chromosome 7. Affected subjects have severe isolated GH deficiency and postnatal growth failure, with a mean adult height of 130 cm for men and 114 cm for women (7-8 standard deviations below the norm). Dwarfism is proportional; a characteristic feature is relative microcephaly, which results in a 'miniaturized adult', eumorphic aspect. Bone age and puberty are delayed, but fertility appears normal. This new syndrome corresponds to the human homologue of the previously identified 'little mouse'.

• Authors: G Baumann
• Journal: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society (Growth Horm IGF Res) Vol. 9 Suppl B Pg. 24-9; discussion 29-30 (Jun 1999) ISSN: 1096-6374 [Print] Scotland
• PMID: 10549302 (Publication Type: Journal Article, Review)

Chemical References

• Codon, Nonsense
• Receptors, Neuropeptide
• Receptors, Pituitary Hormone-Regulating Hormone
• Human Growth Hormone
• somatotropin releasing hormone receptor

Topics

• Adult
• Animals
• Chromosomes, Human, Pair 7 (genetics)
• Codon, Nonsense (genetics)
• Dwarfism, Pituitary (genetics, metabolism)
• Female
• Genes, Recessive
• Human Growth Hormone (deficiency)
• Humans
• Male
• Mice
• Mice, Mutant Strains
• Mutation
• Phenotype
• Point Mutation
• Receptors, Neuropeptide (genetics)
• Receptors, Pituitary Hormone-Regulating Hormone (genetics)
• Syndrome