title: Detection of a recurring mutation in the human growth hormone-releasing hormone receptor gene.
abstract: OBJECTIVE
  Mutations in the gene encoding for the GH-releasing hormone receptor (GHRHR) have been recently described in patients with familial isolated GH deficiency (IGHD) type IB. To date, all reported mutations have been found in kindreds sharing common ancestors. The only exception is a T to A transversion which causes a substitution of histidine for leucine in codon 144 (L144H) and creates a DraIII restriction site. This mutation was described in two families with different ethnic background residing in two different continents (Europe and North America).
  
  
  METHODS
  We searched for GHRHR mutations in a new family with IGHD from a third continent (South America) and found the affected individuals to be homozygous for the same L144H change. We performed linkage analysis with intra- and para-genic polymorphisms to determine if the three families carrying the L144H allele are related.
  
  
  RESULTS
  Linkage analysis studies demonstrated that one of the three families does not share the same para- and intragenic GHRHR polymorphisms with the other two.
  
  
  CONCLUSIONS
  The L144H mutation has arisen at least twice and should be considered for initial genetic analysis in patients with familial IGHD in whom the a GHRHR mutation is suspected.
authors.affiliation: Department of Medicine and The Ilyssa Center for Molecular and Cellular Endocrinology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. salvator@jhmi.edu
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvatori
authors.forename: Manuel H
authors.initials: MH
authors.lastname: Aguiar-Oliveira
authors.forename: Luciana V B
authors.initials: LV
authors.lastname: Monte
authors.forename: Lora
authors.initials: L
authors.lastname: Hedges
authors.forename: Norma L
authors.initials: NL
authors.lastname: Santos
authors.forename: Rossana M C
authors.initials: RM
authors.lastname: Pereira
authors.forename: John A
authors.initials: JA
authors.lastname: Phillips
mesh_terms: D000328:Adult; D001938:Brazil; D002874:Chromosome Mapping; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000172:deficiency*; D013007:Growth Hormone-Releasing Hormone; D006801:Humans; D007328:Insulin; D008297:Male; D009656:North America; D010900:Pituitary Diseases / Q000235:genetics*; D011110:Polymorphism, Genetic; D018013:Receptors, Neuropeptide / Q000235:genetics*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics*; D013030:Spain; D013973:Thyrotropin-Releasing Hormone
chemical_list: D007328:Insulin; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; C039542:somatocrinin receptor; D013973:Thyrotropin-Releasing Hormone; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone