INVESTIGADORES
DOMENE Sabina
artículos
Título:
Assessment of Pathogenicity of natural IGFALS gene variants by in silico bioinformatic tools and in vitro functional studies
Autor/es:
MARTUCCI, LUCIA; GUTIERREZ, MARIANA; KARABATAS, LILIANA; SCAGLIA, PAULA; REY, RODOLFO; DOMENE, HORACIO; JASPER, HECTOR; DOMENE, SABINA
Revista:
MOLECULAR AND CELLULAR ENDOCRINOLOGY.
Editorial:
ELSEVIER IRELAND LTD
Referencias:
Lugar: Amsterdam; Año: 2016 vol. 429 p. 19 - 28
ISSN:
0303-7207
Resumen:
Acid-labile subunit (ALS) is essential for stabilization of IGF-I and IGFBP-3 internary complexes within the vascular system. ALS deficient (ALS-D) patients and a subsetof children with idiopathic short stature (ISS), presenting IGFALS gene variants, showvariable degree of growth retardation associated to IGF-I and IGFBP-3 deficiencies. Theaim of this study was to evaluate the potential pathogenicity of eleven IGFALS variantsidentified in ALS-D and ISS children using in silico and in vitro approaches. We were ableto classify seven of these variants as pathogenic since they present impaired synthesis(p.Glu35Lysfs*87, p.Glu35Glyfs*17, p.Asn276Ser, p.Leu409Phe, p.Ser490Trp andp.Cys540Arg), or partial impairment of synthesis and lack of secretion (p.Leu213Phe). Wealso observed significant reduction of secreted protein for variants p.Ala330Asp,Ala475Val and p.Arg548Trp, while still retaining their ability to form ternary complexes.These findings provide an approach to test the pathogenicity of IGFALS gene variants.