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 language | English |
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Pages (from-to) | 100-10 |
Number of pages | 11 |
Journal | Hormone Research |
Volume | 71 |
Issue number | 2 |
DOIs | |
Publication status | Published - 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