Article

Growth hormone receptor gene mutations in two Italian patients with Laron Syndrome.

Unit of Pediatrics, Department of Medical Sciences, University of Piemonte Orientale, Novara, Italy.
Journal of endocrinological investigation (impact factor: 1.57). 06/2007; 30(5):417-20.
Source: PubMed

ABSTRACT Laron Syndrome (LS) represents a condition characterized by GH insensitivity caused by molecular defects in the GH receptor (GHR) gene or in the post-receptor signalling pathway. We report the molecular characterization of two unrelated Italian girls from Sicily diagnosed with LS. The DNA sequencing of the GHR gene revealed the presence of different nonsense mutations, occurring in the same background haplotype. The molecular defects occurred in the extracellular domain of the GHR leading to a premature termination signal and to a truncated non-functional receptor. In one patient, a homozygous G to T transversion, in exon 6, led to the mutation GAA to TAA at codon 180 (E180X), while in the second patient a homozygous C to T transition in exon 7 was detected, causing the CGA to TAA substitution at codon 217 (R217X). Both probands presented the polymorphisms Gly168Gly and Ile544Leu in a homozygous state in exons 6 and 10, respectively. The E180X represents a novel defect of the GHR gene, while the R217X mutation has been previously reported in several patients from different ethnic backgrounds but all from countries located in the Mediterranean and Middle Eastern region.

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Keywords

different ethnic backgrounds
 
different nonsense mutations
 
exon 6
 
exons 6
 
extracellular domain
 
GH receptor
 
GHR gene
 
Middle Eastern region
 
molecular characterization
 
mutation GAA
 
patients
 
polymorphisms Gly168Gly
 
post-receptor signalling pathway
 
premature termination signal
 
R217X mutation
 
second patient
 
T transversion
 
TAA substitution
 
truncated non-functional receptor
 
unrelated Italian girls