TY - JOUR
T1 - Novel intragenic deletions within the UBE3A gene in two unrelated patients with Angelman syndrome: Case report and review of the literature
AU - Aguilera, Cinthia
AU - Viñas-Jornet, Marina
AU - Baena, Neus
AU - Gabau, Elisabeth
AU - Fernández, Concepción
AU - Capdevila, Nuria
AU - Cirkovic, Sanja
AU - Sarajlija, Adrijan
AU - Miskovic, Marijana
AU - Radivojevic, Danijela
AU - Ruiz, Anna
AU - Guitart, Miriam
PY - 2017/11/21
Y1 - 2017/11/21
N2 - © 2017 The Author(s). Background: 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.
AB - © 2017 The Author(s). Background: 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.
KW - Angelman syndrome (AS)
KW - Intragenic deletions
KW - MLPA
KW - UBE3A
U2 - https://doi.org/10.1186/s12881-017-0500-x
DO - https://doi.org/10.1186/s12881-017-0500-x
M3 - Article
VL - 18
IS - 1
M1 - 137
ER -