Molecular characterization of 21 X-ALD Portuguese families: identification of eight novel mutations in the ABCD1 gene

• Tipo: Artigo em Revista Científica Internacional
• Data: 2002

Autores

guimaraes, cp (Autor) Outra; lemos, m (Autor) Outra; sa-miranda, c (Autor) Outra; azevedo, je (Autor) ICBAS

Revista

Título: Molecular Genetics and Metabolism

Vol. 76

Páginas: 62-67

ISSN: 1096-7192

Editora: Elsevier

Indexação

ISI Web of Knowledge - 8 Citações

Scopus - 9 Citações

Outras Informações

ID Authenticus: P-000-PJC

DOI: 10.1016/S1096-7192(02)00023-9

Abstract (EN): X-linked adrenoleukodystrophy (X-ALD) is the most common inherited peroxisomal disorder. The gene associated with X-ALD, ABCD1, encodes a peroxisomal ATP-binding cassette half-transporter. In this study, we describe the molecular characterization of 21 affected Portuguese families. The complete coding region of the ABCD1 gene was amplified by reverse transcription polymerase chain reaction (RT-PCR) or genomic PCR. After conformation-sensitive gel electrophoresis analysis, fragments with a conformational heteroduplex pattern were sequenced. Using this strategy, we have identified 14 missense mutations, two nonsense mutations, two splicing site defects, and three small deletions, two of them resulting in frameshifts. Eight of the genetic alterations characterized in this Study are novel. The levels of the ABCD1 transcript as well as the levels of ALDP in cultured skill fibroblasts of male probands were also determined in most cases. The levels of the ABCD1 transcript in one patient (corresponding to a nonsense mutation) were below the detection limit of Northern-blotting analysis. ALDP was found at normal levels in only three patients, absent in five (corresponding to a double missense, two nonsense, and two frameshift mutations), and decreased in all the others. (C) 2002 Elsevier Science (USA). All rights reserved.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 6