Assessment of pathogenicity of natural IGFALS gene variants by in silico bioinformatics tools and in vitro functional studies.
Mol Cell Endocrinol
; 429: 19-28, 2016 07 05.
Article
em En
| MEDLINE
| ID: mdl-27018247
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Simulação por Computador
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Glicoproteínas
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Proteínas de Transporte
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Biologia Computacional
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Polimorfismo de Nucleotídeo Único
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
Mol Cell Endocrinol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Argentina