Background: Laron syndrome (LS) is an autosomal recessive disease characterized by severe postnatal growth failure, short stature, normal or elevated serum GH, and low levels of IGF-I and IGF binding protein-3 (IGFBP-3). The disorder is caused by dysfunction of the growth hormone receptor resulted from mutations in GHR gene.
Objective: Purpose of this research was to describe mutations on GHR gene in five children with Laron syndrome.
Methods: Five children who were diagnosed as Laron syndrome according to the clinical and biochemical test results. Genomic DNAs were isolated from their blood by salting out method. The exons and exon/intron boundaries of GHR for each patient were amplified by PCR using specific primers. The PCR products of the exons for GHR were run on agarose gel electrophoresis, purified and sequenced by forward and reverse primers.
Results: We determined one splice site mutation (70+G->A), two missense mutations (I526L and S40L) and exon 3 deletion polymorphism in GHR from Laron children and they are homozygote. Splice site mutation was caused by substitution of G residue of GT consensus sequence in donor splice site to A residue disrupting consensus sequence at intron 2 of GHR. I526L mutation was created by changing of A residue of ATC codon to C residue leading CTC codon encoding to leucine in one child at exon 10 and S40L mutation occurred by changing of C residue of TCA codon encoding serine to T residue at exon 4 leading TTA codon encoding Leucine. However, no mutation in GHR was found in the two children and they are under investigation for mutations in genes located at more downstream of GHR.
Precise conclusions: One splice site mutation and two missense mutation were detected in three laron patient from five children with Laron in Turkish population.
25 - 29 Apr 2009
European Society of Endocrinology