Send to:

Choose Destination
See comment in PubMed Commons below
Horm Res Paediatr. 2012;78(3):165-72. doi: 10.1159/000342760. Epub 2012 Oct 10.

GH-releasing hormone receptor gene: a novel splice-disrupting mutation and study of founder effects.

Author information

  • 1Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, São Paulo, Brazil.



Mutations in GH-releasing hormone receptor gene (GHRHR) are emerging as the most common cause of autosomal recessive isolated GH deficiency (IGHD).


To search for GHRHR mutations in patients with familial or sporadic IGHD and to investigate founder effects in recurring mutations.


The coding region of GHRHR was entirely amplified and sequenced from DNA of 18 patients with IGHD (16 unrelated) with topic posterior pituitary lobe on MRI. Haplotypes containing promoter SNPs and microsatellites flanking GHRHR were analyzed in patients with c.57+1G>A (IVS1+1G>A) mutation of our previously published kindred and also a Brazilian patient and 2 previously reported Japanese sisters with c.1146G>A (p.E382E) mutation.


A novel homozygous intronic GHRHR c.752-1G>A (IVS7-1G>A) mutation, predicting loss of the constitutive splice acceptor site, was identified in two siblings with IGHD. A compound heterozygous c.[57+1G>A];[1146G>A] and a heterozygous c.527C>T (p.A176V) were found in two sporadic cases. Haplotype analysis provided evidence for a founder effect for the c.57+1G>A mutation and independent recurrence for the c.1146G>A mutation.


We report a novel splice-disrupting mutation in GHRHR in 2 siblings and provide evidence that all c.57+1G>A (IVS1+1G>A) mutant chromosomes have the same haplotype ancestor, indicating the occurrence of a founder effect in Brazilian patients with IGHD.

Copyright © 2012 S. Karger AG, Basel.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for S. Karger AG, Basel, Switzerland
    Loading ...
    Write to the Help Desk