title: Three novel IGFALS gene mutations resulting in total ALS and severe circulating IGF-I/IGFBP-3 deficiency in children of different ethnic origins.
abstract: OBJECTIVE
  To date, four mutations in the IGFALS gene have been reported. We now describe two children of different ethnic background with total acid-labile subunit (ALS) and severe circulating IGF-I/IGFBP-3 deficiencies resulting from three novel mutations in the IGFALS gene.
  
  
  METHODS
  Serum and DNA of patients were analyzed.
  
  
  RESULTS
  Case 1 is a 12-year-old boy of Mayan origin. Case 2 is a 5-year-old girl of Jewish/Eastern European (Polish, Russian, Austrian-Hungarian)/Icelandic/European (French, English) ancestry. The reported cases had moderate short stature (-2.91 and -2.14 SDS, respectively), nondetectable serum ALS and extremely low serum concentrations of IGF-I and IGFBP-3. Case 1 harbored a novel homozygous 1308_1316 dup9 mutation in a highly conserved leucine-rich repeat (LRR) 17 motif of exon 2, representing an in-frame insertion of 3 amino acids, LEL. Case 2 harbored a novel heterozygous C60S/L244F mutation in exon 2, located within a highly conserved LRR 1 and LRR 9, respectively.
  
  
  CONCLUSIONS
  The identification of additional novel IGFALS mutations, resulting in severe IGF-I/IGFBP-3 and ALS deficiencies, supports IGFALS as a candidate gene of the GH/IGF system, implicated in the pathogenesis of primary IGF deficiency, and represents an important part of its differential diagnosis.
authors.affiliation: Department of Pediatrics, NRC5, Oregon Health and Science University, Portland, Oreg. 97239, USA. ogambetti@yahoo.com
authors.forename: Olga V
authors.initials: OV
authors.lastname: Fofanova-Gambetti
authors.forename: Vivian
authors.initials: V
authors.lastname: Hwa
authors.forename: Susan
authors.initials: S
authors.lastname: Kirsch
authors.forename: Catherine
authors.initials: C
authors.lastname: Pihoker
authors.forename: Harvey K
authors.initials: HK
authors.lastname: Chiu
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Högler
authors.forename: Laurie E
authors.initials: LE
authors.lastname: Cohen
authors.forename: Christina
authors.initials: C
authors.lastname: Jacobsen
authors.forename: Michael A
authors.initials: MA
authors.lastname: Derr
authors.forename: Ron G
authors.initials: RG
authors.lastname: Rosenfeld
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007197:Indians, Central American; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007585:Jews; D008297:Male; D009154:Mutation
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; C075944:insulin-like growth factor binding protein, acid labile subunit; D007334:Insulin-Like Growth Factor I