An intronic growth hormone receptor mutation causing activation of a pseudoexon is associated with a broad spectrum of growth hormone insensitivity phenotypes.
J Clin Endocrinol Metab
; 92(2): 655-9, 2007 Feb.
Article
in En
| MEDLINE
| ID: mdl-17148568
ABSTRACT
CONTEXT Inherited GH insensitivity (GHI) is usually caused by mutations in the GH receptor (GHR). Patients present with short stature associated with high GH and low IGF-I levels and may have midfacial hypoplasia (typical Laron syndrome facial features). We previously described four mildly affected GHI patients with an intronic mutation in the GHR gene (A(-1)-->G(-1) substitution in intron 6), resulting in the activation of a pseudoexon (6Psi) and inclusion of 36 amino acids. OBJECTIVE:
The study aimed to analyze the clinical and genetic characteristics of additional GHI patients with the pseudoexon (6Psi) mutation. DESIGN/PATIENTS Auxological, biochemical, genetic, and haplotype data from seven patients with severe short stature and biochemical evidence of GHI were assessed. MAIN OUTCOMEMEASURES:
We assessed genotype-phenotype relationship.RESULTS:
One patient belongs to the same extended family, previously reported. She has normal facial features, and her IGF-I levels are in the low-normal range for age. The six unrelated patients, four of whom have typical Laron syndrome facial features, have heights ranging from -3.3 to -6.0 sd and IGF-I levels that vary from normal to undetectable. We hypothesize that the marked difference in biochemical and clinical phenotypes might be caused by variations in the splicing efficiency of the pseudoexon.CONCLUSIONS:
Activation of the pseudoexon in the GHR gene can lead to a variety of GHI phenotypes. Therefore, screening for the presence of this mutation should be performed in all GHI patients without mutations in the coding exons.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carrier Proteins
/
Pseudogenes
/
Human Growth Hormone
/
Growth Disorders
Type of study:
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
/
Male
Language:
En
Journal:
J Clin Endocrinol Metab
Year:
2007
Document type:
Article
Affiliation country:
Reino Unido