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Journal of Endocrinological Investigation

, Volume 29, Issue 2, pp 122–130 | Cite as

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

  • O. Haskin
  • L. Lazar
  • L. Jaber
  • R. Salvatori
  • M. Alba
  • L. Kornreich
  • M. PhillipEmail author
  • G. Gat-Yablonski
Original Articles

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.

En]Keywords

IGHD GHRH receptor mutation 

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Copyright information

© Italian Society of Endocrinology (SIE) 2006

Authors and Affiliations

  • O. Haskin
    • 1
  • L. Lazar
    • 1
  • L. Jaber
    • 2
    • 3
  • R. Salvatori
    • 4
  • M. Alba
    • 4
  • L. Kornreich
    • 5
  • M. Phillip
    • 1
    Email author
  • G. Gat-Yablonski
    • 1
  1. 1.Institute for Endocrinology and Diabetes, National Center for Childhood DiabetesSchneider Children’s Medical Center of IsraelPetah TikvaIsrael
  2. 2.Day Care Clinic and Emergency Medicine DepartmentIsrael
  3. 3.Bridge to Peace Community Pediatric CenterTaibeIsrael
  4. 4.Division of Endocrinology and The Ilyssa Center for Molecular and Cellular EndocrinologyThe Johns Hopkins University School of MedicineBaltimoreUSA
  5. 5.Imaging DepartmentSchneider Children’s Medical Center of Israel and Felsenstein Medical Research CenterTel Aviv

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