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

BMC Medical Genetics

Case Report

Adrijan Sarajlija¹  Cinthia Aguilera²  Anna Ruiz²  Marina Viñas-Jornet²  Miriam Guitart²  Neus Baena²  Sanja Cirkovic³  Danijela Radivojevic³  Marijana Miskovic³  Nuria Capdevila⁴  Elisabeth Gabau⁴  Concepción Fernández⁴ 

[1] Department of Metabolism and Clinical Genetics, Mother and Child Health Care Institute of Serbia “Dr Vukan Cupic“, Belgrade, Serbia;School of Medicine, University of Belgrade, Belgrade, Serbia;Genetics Laboratory, UDIAT-Centre Diagnòstic, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Parc del Taulí 1, 08208, Barcelona, Sabadell, Spain;Laboratory for Medical Genetics, Mother and Child Health Care Institute of Serbia “Dr Vukan Cupic”, Belgrade, Serbia;Paediatric Unit, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain;

关键词: Angelman syndrome (AS);    UBE3A;    Intragenic deletions;    MLPA;   

DOI  :  10.1186/s12881-017-0500-x

 received in 2017-02-28, accepted in 2017-11-14,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundPatients 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 presentationWe 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.ConclusionAlthough 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.

【 授权许可】

CC BY   
© The Author(s). 2017