Identification of a de novo splicing variant in the Coffin-Siris gene, SMARCE1, in a patient with Angelman-like syndrome

Aguilera, CinthiaGabau, ElisabethLaurie, Steven, 1973-Baena, NeusDerdak, SophiaCapdevila, NúriaRamirez, AriadnaDelgadillo, VeronicaGarcía-Catalan, Maria JesusBrun i Gasca, CarmeGuitart, MiriamRuiz, Anna2019-03-082019-03-082019Aguilera C, Gabau E, Laurie S, Baena N, Derdak S, Capdevila N, Ramirez A, Delgadillo V, García-Catalan MJ, Brun C, Guitart M, Ruiz A. Identification of a de novo splicing variant in the Coffin-Siris gene, SMARCE1, in a patient with Angelman-like syndrome. Mol Genet Genomic Med. 2019; 7(1):e00511. DOI 10.1002/mgg3.5112324-9269http://hdl.handle.net/10230/36778Background: 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. Methods: 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. Results: 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. Conclusions: 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.application/pdfeng© 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Identification of a de novo splicing variant in the Coffin-Siris gene, SMARCE1, in a patient with Angelman-like syndromeinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1002/mgg3.511Angelman syndrome (AS)Coffin–Siris syndrome (CSS)Exome sequencingSMARCE1info:eu-repo/semantics/openAccess