Open AccessIdentification of a de novo splicing variant in the Coffin–Siris gene, SMARCE 1, in a patient with Angelman‐like syndrome
Author(s) -
Aguilera Cinthia,
Gabau Elisabeth,
Laurie Steve,
Baeeus,
Derdak Sophia,
Capdevila Núria,
Ramirez Ariadna,
Delgadillo Veronica,
GarcíaCatalan Maria Jesus,
Brun Carme,
Guitart Miriam,
Ruiz Anna
Publication year - 2019
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.511
Subject(s) - angelman syndrome , genetics , exon , exome sequencing , missense mutation , intellectual disability , omim : online mendelian inheritance in man , rna splicing , medicine , ataxia , phenotype , bioinformatics , gene , biology , psychiatry , rna
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 SMARCE 1 splicing variant that leads to an exon skipping in a patient with an Angelman‐like phenotype. Missense variants in the SMARCE 1 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 .