title: Polymorphisms identified in the upstream core polyadenylation signal of IGF1 gene exon 6 do not cause pre- and postnatal growth impairment.
abstract: BACKGROUND
  Few children born small for gestational age (SGA) with IGF1 mutations have been reported. One of these patients presented a mutation at 3' untranslated region (UTR) at exon 6, probably affecting the polyadenylation process.
  
  
  OBJECTIVE
  The objective of the study was to sequence the IGF1 gene of children born SGA.
  
  
  METHODS
  IGF1 (exons 1-6) was directly sequenced in 53 SGA children without catch-up growth. Allelic variant frequency of the identified IGF1 polymorphisms was assessed in a total of 145 SGA children and in 180 controls born with adequate weight and length and adult height sd score greater than -2.
  
  
  RESULTS
  No mutations were identified in the IGF1 coding regions in SGA children. In contrast, six allelic variants were identified in the upstream core polyadenylation signal located in IGF1 3' UTR at exon 6. The frequency of the different allelic variants was similar in SGA children and controls. It is noteworthy that the same allelic variant, previously described as causing severe IGF1 deficiency, was also observed in homozygous (n = 4) and heterozygous state (n = 6) in normal height controls, corresponding to 4% of studied alleles. The three most frequently identified allelic variants of IGF1 3' UTR showed no effect on height sd score of adult controls as well as on birth characteristics in SGA children.
  
  
  CONCLUSIONS
  The polymorphisms identified in the upstream core polyadenylation signal at IGF1 exon 6 do not cause IGF1 deficiency as well as pre- and postnatal growth impairment, in contrast to previously reported data.
authors: Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia do Desenvolvimento, 05403-900 Sao Paulo, Brazil.
authors: Debora C
authors: DC
authors: Coutinho
authors: Rocio R D
authors: RR
authors: Coletta
authors: Elaine M F
authors: EM
authors: Costa
authors: Paulo R
authors: PR
authors: Pachi
authors: Margaret C S
authors: MC
authors: Boguszewski
authors: Durval
authors: D
authors: Damiani
authors: Berenice B
authors: BB
authors: Mendonca
authors: Ivo J P
authors: IJ
authors: Arnhold
authors: Alexander A L
authors: AA
authors: Jorge
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000483:Alleles; D002648:Child; D004247:DNA / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D026723:Polyadenylation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D007334:Insulin-Like Growth Factor I; D004247:DNA