Phenotype: Genotype relationships in growth hormone insensitivity syndrome

Kathryn (Katie) Woods, Florence Dastot, Michael A. Preece, Adrian J L Clark, Marie Catherine Postel-Vinay, Pierre G. Chatelain, Michael B. Ranke, Ronald (Ron) Rosenfeld, Serge Amselem, Martin O. Savage

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

GH insensitivity syndrome (GHIS) is associated with many different mutations of the GH receptor (GHR) gene. We examined the phenotypic and biochemical features in 82 GHIS patients from 23 countries, each fulfilling diagnostic criteria of GHIS. There were 45 males and 37 females [mean age, 8.25 yr; mean height, -6.09 SD score, and mean insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3), -7.99 SD score]. Sixty-three were GH- binding protein (GHBP) negative; 19 were GHBP positive (>10% binding). The mean height in GHBP-negative subjects was -6.5% SD score, and that in GHBP- positive patients was -4.9 SD score (P = 2 = 0.45; P = 2 = 0.01). Fifteen different GH receptor gene mutations were identified in 27 patients. All had homozygous defects, except 1 who had a compound heterozygous defect. The mutations were 5 nonsense, 2 frame shift, 4 splice, 4 missense, and 1 compound heterozygote. There was no relationship between mutation type or exon of the GHR gene involved and height or IGFBP-3 SD score. In conclusions, GHIS is associated with wide variation in the severity of clinical and biochemical phenotypes. This variation cannot clearly be accounted for by defects in the GHR gene. Other genetic and/or environmental factors must, therefore, contribute to phenotype in GHIS.

Original languageEnglish (US)
Pages (from-to)3529-3535
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume82
Issue number11
StatePublished - 1997
Externally publishedYes

Fingerprint

Laron Syndrome
Growth Hormone
Genes
Genotype
Phenotype
Insulin-Like Growth Factor Binding Protein 3
Mutation
Defects
Exons
Heterozygote
somatotropin-binding protein

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Woods, K. K., Dastot, F., Preece, M. A., Clark, A. J. L., Postel-Vinay, M. C., Chatelain, P. G., ... Savage, M. O. (1997). Phenotype: Genotype relationships in growth hormone insensitivity syndrome. Journal of Clinical Endocrinology and Metabolism, 82(11), 3529-3535.

Phenotype : Genotype relationships in growth hormone insensitivity syndrome. / Woods, Kathryn (Katie); Dastot, Florence; Preece, Michael A.; Clark, Adrian J L; Postel-Vinay, Marie Catherine; Chatelain, Pierre G.; Ranke, Michael B.; Rosenfeld, Ronald (Ron); Amselem, Serge; Savage, Martin O.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 82, No. 11, 1997, p. 3529-3535.

Research output: Contribution to journalArticle

Woods, KK, Dastot, F, Preece, MA, Clark, AJL, Postel-Vinay, MC, Chatelain, PG, Ranke, MB, Rosenfeld, RR, Amselem, S & Savage, MO 1997, 'Phenotype: Genotype relationships in growth hormone insensitivity syndrome', Journal of Clinical Endocrinology and Metabolism, vol. 82, no. 11, pp. 3529-3535.
Woods KK, Dastot F, Preece MA, Clark AJL, Postel-Vinay MC, Chatelain PG et al. Phenotype: Genotype relationships in growth hormone insensitivity syndrome. Journal of Clinical Endocrinology and Metabolism. 1997;82(11):3529-3535.
Woods, Kathryn (Katie) ; Dastot, Florence ; Preece, Michael A. ; Clark, Adrian J L ; Postel-Vinay, Marie Catherine ; Chatelain, Pierre G. ; Ranke, Michael B. ; Rosenfeld, Ronald (Ron) ; Amselem, Serge ; Savage, Martin O. / Phenotype : Genotype relationships in growth hormone insensitivity syndrome. In: Journal of Clinical Endocrinology and Metabolism. 1997 ; Vol. 82, No. 11. pp. 3529-3535.
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