[Founder effect of E180splice mutation in growth hormone receptor gene (GHR) identified in Brazilian patients with GH insensitivity].
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.
Laboratório de Hormônios e Genética Molecular LIM/42, Faculdade de Medicina, Universidade de São Paulo, SP. alexj@usp.br
Alexander A de Lima
AA
Jorge
Hamilton C de
HC
Menezes Filho
Theresa S Soares
TS
Lins
Dulce Rondini
DR
Guedes
Durval
D
Damiani
Nuvarte
N
Setian
Ivo J Prado
IJ
Arnhold
Berenice B de
BB
Mendonça
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D002835:Christianity; D004484:Ecuador; D005091:Exons / Q000235:genetics; D005260:Female; D018703:Founder Effect; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007557:Israel; D007585:Jews; D046150:Laron Syndrome / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011986:Receptors, Somatotropin / Q000235:genetics*
D011986:Receptors, Somatotropin; D019382:Human Growth Hormone