Novel deletion of the E3A ubiquitin protein ligase gene detected by multiplex ligation-dependent probe amplification in a patient with Angelman syndrome

Francesco Calì, Alda Ragalmuto, Valeria Chiavetta, Giuseppe Calabrese, Marco Fichera, Mirella Vinci, Giuseppa Ruggeri, Pietro Schinocca, Maurizio Sturnio, Salvatore Romano, Valentino Romano, Maurizio Elia

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)842-848
Number of pages7
JournalExperimental and Molecular Medicine
Volume42
Issue number12
DOIs
Publication statusPublished - Dec 2010

Keywords

  • Angelman syndrome
  • Gene dosage
  • Genetic association studies
  • Ubiquitin-protein ligases

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Clinical Biochemistry

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