Detection of heterozygous deletions and duplications in the MECP2 gene in Rett syndrome by Robust Dosage PCR (RD-PCR)

• Autor(a) principal: Shi, Jinxiu
• Data de Publicação: 2005
• Outros Autores: Shibayama, Akane, Liu, Qiang, Nguyen, Vu Q., Feng, Jinong, Santos, Mónica, Temudo, Teresa, Maciel, P., Sommer, Steve S.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/1822/2942
• topic: Rett syndrome; MECP2; RD-PCR; Heterozygous deletion

Fifty to eighty percent of Rett syndrome (RTT) cases have point mutations in the gene encoding methyl-CpG-binding protein-2 (MECP2). A fraction of MECP2 negative classical RTT patients has large heterozygous deletions. Robust Dosage PCR (RD-PCR) assays were developed as a rapid, convenient and accurate method to detect large heterozygous deletions and duplications. A blinded analysis was performed for 65 RTT cases from Portugal by RDPCR in the coding exons 2-4 of the MECP2 gene. Neither the patients with point mutations nor the non-classical RTT patients without point mutation had a deletion or duplication. One of remaining eight female patients with classical RTT without point mutation had a heterozygous deletion. This is the first report of a deletion spanning the entire MECP2 gene. The deletion was confirmed by southern blotting analysis and the deletion junction was localized 37kb upstream from exon 1 and 18kb downstream from exon 4. No duplications were detected. Our results suggest that RD-PCR is an accurate and convenient molecular diagnostic method.