Artículo
Assessment of pathogenicity of natural IGFALS gene variants by in silico bioinformatics tools and in vitro functional studies
Martucci, Lucia Camila
; Gutiérrez, Mariana Lilián
; Karabatas, Liliana Margarita
; Scaglia, Paula Alejandra
; Rey, Rodolfo Alberto
; Domene, Horacio Mario
; Jasper, Hector Guillermo
; Domene, Sabina
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Fecha de publicación:
07/2016
Editorial:
Elsevier Ireland
Revista:
Molecular and Cellular Endocrinology
ISSN:
0303-7207
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Acid-labile subunit (ALS) is essential for stabilization of IGF-I and IGFBP-3 in ternary complexes within the vascular system. ALS deficient (ALS-D) patients and a subset of children with idiopathic short stature (ISS), presenting IGFALS gene variants, show variable degree of growth retardation associated to IGF-I and IGFBP-3 deficiencies. The aim of this study was to evaluate the potential pathogenicity of eleven IGFALS variants identified in ALS-D and ISS children using in silico and in vitro approaches. We were able to classify seven of these variants as pathogenic since they present impaired synthesis (p.Glu35Lysfs*87, p.Glu35Glyfs*17, p.Asn276Ser, p.Leu409Phe, p.Ser490Trp and p.Cys540Arg), or partial impairment of synthesis and lack of secretion (p.Leu213Phe). We also 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.
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Articulos(CEDIE)
Articulos de CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Articulos de CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Citación
Martucci, Lucia Camila; Gutiérrez, Mariana Lilián; Karabatas, Liliana Margarita; Scaglia, Paula Alejandra; Rey, Rodolfo Alberto; et al.; Assessment of pathogenicity of natural IGFALS gene variants by in silico bioinformatics tools and in vitro functional studies; Elsevier Ireland; Molecular and Cellular Endocrinology; 429; 7-2016; 19-28
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