Novel intragenic deletions within the UBE3A gene in two unrelated patients with Angelman syndrome: Case report and review of the literature

Aguilera, Cinthia (57197770702)Cinthia (57197770702)AguileraViñas-Jornet, Marina (57191571579)Marina (57191571579)Viñas-JornetBaena, Neus (6601957933)Neus (6601957933)BaenaGabau, Elisabeth (6603135088)Elisabeth (6603135088)GabauFernández, Concepción (56597410500)Concepción (56597410500)FernándezCapdevila, Nuria (57197775137)Nuria (57197775137)CapdevilaCirkovic, Sanja (56627166200)Sanja (56627166200)CirkovicSarajlija, Adrijan (26027638400)Adrijan (26027638400)SarajlijaMiskovic, Marijana (53164410600)Marijana (53164410600)MiskovicRadivojevic, Danijela (12769357500)Danijela (12769357500)RadivojevicRuiz, Anna (57203664257)Anna (57203664257)RuizGuitart, Miriam (6701410535)Miriam (6701410535)Guitart2025-07-022025-07-022017https://doi.org/10.1186/s12881-017-0500-xhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85034631823&doi=10.1186%2fs12881-017-0500-x&partnerID=40&md5=9548f26579fe927d535a0641f89573d5https://remedy.med.bg.ac.rs/handle/123456789/13159Background: Patients with Angelman syndrome (AS) are affected by severe intellectual disability with absence of speech, distinctive dysmorphic craniofacial features, ataxia and a characteristic behavioral phenotype. AS is caused by the lack of expression in neurons of the UBE3A gene, which is located in the 15q11.2-q13 imprinted region. Functional loss of UBE3A is due to 15q11.2-q13 deletion, mutations in the UBE3A gene, paternal uniparental disomy and genomic imprinting defects. Case presentation: We report here two patients with clinical features of AS referred to our hospital for clinical follow-up and genetic diagnosis. Methylation Specific-Multiplex Ligation-Dependent Probe Amplification (MS-MLPA) of the 15q11.2-q13 region was carried out in our laboratory as the first diagnostic tool detecting two novel UBE3A intragenic deletions. Subsequently, the MLPA P336-A2 kit was used to confirm and determine the size of the UBE3A deletion in the two patients. A review of the clinical features of previously reported patients with whole UBE3A gene or partial intragenic deletions is presented here together with these two new patients. Conclusion: Although rare, UBE3A intragenic deletions may represent a small fraction of AS patients without a genetic diagnosis. Testing for UBE3A intragenic exonic deletions should be performed in those AS patients with a normal methylation pattern and no mutations in the UBE3A gene. © 2017 The Author(s).Angelman syndrome (AS)Intragenic deletionsMLPAUBE3ANovel intragenic deletions within the UBE3A gene in two unrelated patients with Angelman syndrome: Case report and review of the literature