Comprehensive Genetic Analysis and Structural Characterization of CYP21A2 Mutations in CAH Patients

• Tipo: Artigo em Revista Científica Internacional
• Data: 2012

Autores

Carvalho, B (Autor) Outra; Pereira, M (Autor) Outra; Marques, CJ (Autor) FMUP; Carvalho, Davide (Autor) FMUP; Leao, M (Autor) Outra; João Paulo Oliveira (Autor) FMUP; barros, a (Autor) FMUP; carvalho, f (Autor) FMUP

Revista

Título: EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES

Vol. 120

Páginas: 535-539

ISSN: 0947-7349

Indexação

ISI Web of Knowledge - 9 Citações

Scopus - 9 Citações

Outras Informações

ID Authenticus: P-002-4MZ

DOI: 10.1055/s-0032-1323805

Abstract (EN): Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder caused by mutations in the steroid 21-hydroxylase gene (CYP21A2). Complete DNA sequencing of CYP21A2 was performed in 5 patients, 3 non-classic and 2 classic forms of the disease, that were previously screened for the 10 most common mutations, in order to detect additional mutations that could justify the phenotype of the patients. 5 mutations were identified with the whole gene extended analysis. The mutations, p.Pro432Leu and p.Ala434Glu, the first previously reported by our group and the second a novel one were structurally analyzed with ICM-Pro software regarding biochemical properties such as protein stability, accessibility to surface and hydrophobicity, in order to elucidate their effects on the CYP21A2 protein. The 2 affected residues, Pro432 and Ala434, were also studied for conservation purposes in order to predict the severity of both mutations with PolyPhen-2 software and were considered as "probably damaging". Prediction of clinical severity, based on molecular modelling and sequence conservation, was in accordance with the patient's clinical diagnosis.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 5