Aguilera Cinthia, Gabau Elisabeth, Laurie Steve, Baena Neus, Derdak Sophia, Capdevila Núria, Ramirez Ariadna, Delgadillo Veronica, García-Catalan Maria Jesus, Brun Carme, Guitart Miriam, Ruiz Anna
Genetics Laboratory, UDIAT-Centre Diagnòstic, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain.
Paediatric Unit, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain.
Mol Genet Genomic Med. 2019 Jan;7(1):e00511. doi: 10.1002/mgg3.511. Epub 2018 Dec 11.
Patients affected by Angelman syndrome (AS) present severe intellectual disability, lack of speech, ataxia, seizures, abnormal electroencephalography (EEG), and a characteristic behavioral phenotype. Around 10% of patients with a clinical diagnosis of AS (AS-like) do not have an identifiable molecular defect. Some of these patients harbor alternative genetic defects that present overlapping features with AS.
Trio whole-exome sequence was performed on patient and parent's DNA extracted from peripheral blood. Exome data were filtered according to a de novo autosomal dominant inheritance. cDNA analysis was carried out to assess the effect of the splice site variant.
We identified a novel heterozygous SMARCE1 splicing variant that leads to an exon skipping in a patient with an Angelman-like phenotype. Missense variants in the SMARCE1 gene are known to cause Coffin-Siris syndrome (CSS), which is a rare congenital syndrome. Clinical reevaluation of the patient confirmed the presence of characteristic clinical features of CSS, many of them overlapping with AS.
Taking into account the novel finding reported in this study, we consider that CSS should be added to the expanding list of differential diagnoses for AS.
患有天使综合征（AS）的患者存在严重智力残疾、言语缺失、共济失调、癫痫发作、脑电图（EEG）异常以及特征性的行为表型。临床诊断为AS（AS样）的患者中约10%没有可识别的分子缺陷。其中一些患者存在与AS具有重叠特征的其他遗传缺陷。
对从外周血中提取的患者及其父母的DNA进行三联体全外显子测序。根据新发常染色体显性遗传对外显子数据进行筛选。进行cDNA分析以评估剪接位点变异的影响。
我们在一名具有天使样表型的患者中鉴定出一种导致外显子跳跃的新型杂合SMARCE1剪接变异。已知SMARCE1基因中的错义变异会导致科芬-西里斯综合征（CSS），这是一种罕见的先天性综合征。对该患者的临床重新评估证实存在CSS的特征性临床特征，其中许多与AS重叠。
考虑到本研究报告的新发现，我们认为CSS应添加到AS不断扩大的鉴别诊断列表中。
