CONICET | Buscador de Institutos y Recursos Humanos

Larons Syndrome (LS) is a hereditary form of growth hormone (GH) resistance due to molecular defects in the GH receptor (GHR). The study describes two unrelated patients of Córdoba-Argentina of Hispanic origin with sever short stature.Subjects and method: The patients were examined at 5 and 7 months of CA shown depressed nasal bridge, prominent forehead, mid-facial hypoplasia, excess of subcutaneous fat, high-pitched voices, micropenis, deafness and hypoglicaemia. Genomic DNA was isolated from peripheral blood leukocytes, exon-specific PCR and automatic sequenciation were performed.Results:PATIENT Height SDS GH ng/ml IGF I SDS IGFBP3ng/ml GHBP pmol/lWB -8,6 49 -7,5 50 <10OJ -5,2 45 -3,3 380 <10Molecular studies of all exons of GHR revealed a mutation in exon 7. We observed in both patients homozigosity for a C to T transition in the third position of codon 223. Conclusions: This mutation is similar to that previously described in a Bahamian genetic isolate of Anglo-Saxon origin with extreme short stature and in one Hispanic patient. The mutation creates a preferred splice donor site that alters normal GHR mRNA processing and eliminates 21 amino acids from the extracelular domain. This is the responsible for the GH insensitivity in these patients. The undetectable levels of GHBP would indicate that the mutant protein of GHR was not produced, although the presence of a shorter mRNA corresponding to the transcription of mutant GHR allele was previously demonstrated. The fact that we found the same infrequent mutation in two unrelated patients would suggest that we should consider this mutation when studying other patients with LS from our region.