A new mutation in the growth hormone-releasing hormone receptor gene in two Israeli Arab families

O. Haskin, L. Lazar, L. Jaber, Roberto Salvatori, M. Alba, L. Kornreich, Moshep Phillip, G. Gat-Yablonski

Research output: Contribution to journalArticle

Abstract

Background: Mutations in the GHRH receptor gene (GHRH-R) are emerging as a common cause of familial isolated GH deficiency (IGHD). Design: We searched for GHRH-R mutations in 10 patients with IGHD of Israeli-Arab origin, belonging to two highly consanguineous families. Methods: Analysis of the 13 coding exons, the intron-exon boundaries, and the proximal promoter of the GHRH-R was performed by denaturing gradient gel electrophoresis. Abnormally migrating bands were sequenced. The newly found mutation was inserted into GHRH-R cDNA. Wild type and mutant receptor were expressed in Chinese hamster ovary (CHO) cells, and the cAMP response to GHRH was measured. Results: All patients were homozygous for a novel GHRH-R missense mutation in exon 11 that replaces arginine with cysteine (R357C). Functional assay demonstrated complete inactivity of the mutant receptor in vitro. The prevalence of the mutant allele in the Israeli-Arab population was found to be 2%. All the patients had low but detectable GH reserve, proportionate short stature, and growth retardation since early childhood, with good growth response to GH treatment. Magnetic resonance imaging, performed in 3 patients, revealed a normal sized anterior pituitary in one patient evaluated at early childhood, and a borderline hypoplastic gland in the 2 patients evaluated at puberty. Conclusions: We describe a novel missense mutation in the GHRH-R. The high incidence of the mutant allele in Israeli Arabs suggests that the mutation may be a common cause of familial IGHD in this population.

Original languageEnglish (US)
Pages (from-to)122-130
Number of pages9
JournalJournal of Endocrinological Investigation
Volume29
Issue number2
StatePublished - Feb 2006

Fingerprint

Pituitary Dwarfism
Mutation
Genes
Exons
Missense Mutation
Alleles
Denaturing Gradient Gel Electrophoresis
Puberty
Growth
Cricetulus
Introns
Population
Cysteine
Arginine
somatotropin releasing hormone receptor
Ovary
Complementary DNA
Magnetic Resonance Imaging
Incidence
Therapeutics

Keywords

  • GHRH receptor
  • IGHD
  • Mutation

ASJC Scopus subject areas

  • Endocrinology

Cite this

Haskin, O., Lazar, L., Jaber, L., Salvatori, R., Alba, M., Kornreich, L., ... Gat-Yablonski, G. (2006). A new mutation in the growth hormone-releasing hormone receptor gene in two Israeli Arab families. Journal of Endocrinological Investigation, 29(2), 122-130.

A new mutation in the growth hormone-releasing hormone receptor gene in two Israeli Arab families. / Haskin, O.; Lazar, L.; Jaber, L.; Salvatori, Roberto; Alba, M.; Kornreich, L.; Phillip, Moshep; Gat-Yablonski, G.

In: Journal of Endocrinological Investigation, Vol. 29, No. 2, 02.2006, p. 122-130.

Research output: Contribution to journalArticle

Haskin, O, Lazar, L, Jaber, L, Salvatori, R, Alba, M, Kornreich, L, Phillip, M & Gat-Yablonski, G 2006, 'A new mutation in the growth hormone-releasing hormone receptor gene in two Israeli Arab families', Journal of Endocrinological Investigation, vol. 29, no. 2, pp. 122-130.
Haskin, O. ; Lazar, L. ; Jaber, L. ; Salvatori, Roberto ; Alba, M. ; Kornreich, L. ; Phillip, Moshep ; Gat-Yablonski, G. / A new mutation in the growth hormone-releasing hormone receptor gene in two Israeli Arab families. In: Journal of Endocrinological Investigation. 2006 ; Vol. 29, No. 2. pp. 122-130.
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