1. [Founder effect of E180splice mutation in growth hormone receptor gene (GHR) identified in Brazilian patients with GH insensitivity].
- Author
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Jorge AA, Menezes Filho HC, Lins TS, Guedes DR, Damiani D, Setian N, Arnhold IJ, and Mendonça BB
- Subjects
- Adolescent, Adult, Amino Acid Sequence, Base Sequence, Brazil, Child, Child, Preschool, Christianity, Ecuador, Exons genetics, Female, Humans, Israel, Jews, Laron Syndrome diagnosis, Male, Polymerase Chain Reaction, Founder Effect, Human Growth Hormone deficiency, Laron Syndrome genetics, Mutation genetics, Receptors, Somatotropin genetics
- Abstract
We studied the growth hormone receptor (GHR) gene in 6 patients with Laron syndrome (LS) from 4 unrelated families. Exons 2 to 10 were amplified by PCR using specific intronic pairs of primers. The PCR products were directly sequenced. Our results showed that all 6 patients carried a homozygous GAG>GAA mutation in codon 180 of exon 6. This mutation did not change the translated amino acid, but created an abnormal splice site deleting 8 amino acids from the extracellular domain of GHR. Members of all 4 kindreds with the E180splice mutation were genotyped for 4 polymorphic intragenic sites: The retention or exclusion of exon 3, single nucleotide polymorphisms present in exons 6 and 10, and intron 9 polymorphic site. All 6 patients presented the same haplotype. The E180splice mutation was first described in a population of Spanish descendants from the Andes of Southern Ecuador. This mutation was also found in oriental Jewish patients from Israel. Our families share the same intron-9 haplotype observed in Ecuadorian and Israeli patients. We conclude that the E180splice mutation is an important cause of LS in Brazil and there is probably a founder effect since our patients, Ecuadorian and Israeli patients share the same haplotype in intron 9.
- Published
- 2005
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