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KMID : 0620920100420120842
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Experimental & Molecular Medicine
2010 Volume.42 No. 12 p.842 ~ p.848
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Novel deletion of the E3A ubiquitin protein ligase gene detected by multiplex ligation-dependent probe amplification in a patient with Angelman syndrome
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Cali Francesco
Ragalmuto Alda
Chiavetta Valeria
Calabrese Giuseppe
Fichera Marco
Vinci Mirella
Ruggeri Giuseppa
Schinocca Pietro
Sturnio Maurizio
Romano Salvatore
Romano Valentino
Elia Maurizio
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Abstract
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Angelman syndrome (AS) is a severe neurobehavioural disorder caused by failure of expression of the maternal copy of the imprinted domain located on 15q11-q13. There are different mechanisms leading to AS: maternal microdeletion, uniparental disomy, defects in a putative imprinting centre, mutations of the E3 ubiquitin protein ligase (UBE3A) gene. However, some of suspected cases of AS are still scored negative to all the latter mutations. Recently, it has been shown that a proportion of negative cases bear large deletions overlapping one or more exons of the UBE3A gene. These deletions are difficult to detect by conventional gene-scanning methods due to the masking effect by the non-deleted allele. In this study, we have used for the first time multiplex ligation-dependent probe amplification (MLPA) and comparative multiplex dosage analysis (CMDA) to search for large deletions affecting the UBE3A gene. Using this approach, we identified a novel causative deletion involving exon 8 in an affected sibling. Based on our results, we propose the use of MLPA as a fast, accurate and inexpensive test to detect large deletions in the UBE3A gene in a small but significant percentage of AS patients.
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KEYWORD
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Angelman syndrome, gene dosage, genetic association studies, ubiquitin-protein ligases
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