Three novel IGFALS gene mutations resulting in total ALS and severe circulating IGF-I/IGFBP-3 deficiency in children of different ethnic origins

Olga V Fofanova-Gambetti, Vivian Hwa, Susan Kirsch, Catherine Pihoker, Harvey K Chiu, Wolfgang Högler, Laurie E Cohen, Christina Jacobsen, Michael A Derr, Ron G Rosenfeld

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

BACKGROUND/AIMS: 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.

PATIENTS/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.

Original languageEnglish
Pages (from-to)100-10
Number of pages11
JournalHormone Research
Volume71
Issue number2
DOIs
Publication statusPublished - 2009

Keywords

  • Carrier Proteins
  • Child
  • Child, Preschool
  • Female
  • Genetic Diseases, Inborn
  • Glycoproteins
  • Humans
  • Indians, Central American
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I
  • Jews
  • Male
  • Mutation
  • Case Reports
  • Journal Article

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