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 journalArticle

29 Scopus citations

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 (US)
Pages (from-to)100-110
Number of pages11
JournalHormone Research
Volume71
Issue number2
DOIs
StatePublished - Feb 2009

Keywords

  • Acid-labile subunit deficiency
  • IGFALS gene mutations
  • Primary IGF deficiency

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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    Fofanova-Gambetti, O. V., Hwa, V., Kirsch, S., Pihoker, C., Chiu, H. K., Högler, W., Cohen, L. E., Jacobsen, C., Derr, M. A., & Rosenfeld, R. G. (2009). Three novel IGFALS gene mutations resulting in total ALS and severe circulating IGF-I/IGFBP-3 deficiency in children of different ethnic origins. Hormone Research, 71(2), 100-110. https://doi.org/10.1159/000183899