Large genomic mutations within the ATM gene detected by MLPA, including a duplication of 41 kb from exon 4 to 20.
Ann Hum Genet
; 72(Pt 1): 10-8, 2008 Jan.
Article
em En
| MEDLINE
| ID: mdl-17910737
ABSTRACT
Mutation detection remains problematic for large genes, primarily because PCR-based methodology fails to detect heterozygous deletions and any duplication. In the ATM gene only a handful of multi-exon deletions have been described to date, and this type of mutation has been considered rare. To address this issue we tested a new MLPA (Multiplex Ligation Probe Amplification) kit that covers 33 of the 66 ATM exons, using for controls two previously characterized genomic deletions in addition to three A-T patients, taken from a survey of nine, who had missing four mutations unidentified after conventional mutation screening. We identified for the first time 1) a approximately 41 kb genomic duplication spanning exons 4-20 (c.-30_2816dup41kb)(a.k.a., ATM dup 41 kb); 2) a novel genomic deletion including exon 31, and 3) in hemizygosis a point mutation in the non-deleted exon 31. In this study we extended mutation detection to nine new Italian A-T patients, using a combined approach of haplotype analysis, DHPLC and MLPA. Overall we achieved a mutation detection rate of >97%, and can now define a spectrum of ATM mutations based on twenty-one consecutive Italian families with A-T.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Éxons
/
Proteínas Serina-Treonina Quinases
/
Proteínas de Ciclo Celular
/
Duplicação Gênica
/
Técnicas de Amplificação de Ácido Nucleico
/
Proteínas Supressoras de Tumor
/
Proteínas de Ligação a DNA
/
Mutação
Tipo de estudo:
Observational_studies
Limite:
Humans
Idioma:
En
Revista:
Ann Hum Genet
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Itália