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

Abstract

Background 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.

Genetic investigation of the ubiquitin-protein ligase E3A gene as putative target in Angelman syndrome

“…Some of these patients have genetic variations that exhibit overlapping features with AS. Hence, we need next-generation sequencing (NGS) as one of the fastest techniques to screen other genes responsible for the development of these disorders[ 15 ]. The integration of whole-exome and whole-genome sequencing, along with high-throughput genotyping and linkage analysis, may contribute to the identification of new genes linked to AS-like syndromes.…”