ABSTRACT
Objective
To explore the clinical presentation and genetic etiology of a child with intellectual disability, speech developmental delay, learning difficulties, behavioral stereotype, and obsessive-compulsive disorder, and to identify new variants.
Methods and Results
In this study, Karyotype and copy number variant sequencing (CNV-seq) were performed to detect chromosome abnormalities in this family. The whole exome sequencing (WES) was performed to investigate additional genetic variants in this family. Minigene array was used to verify whether the novel variant c.1027-2A>G really affected the splicing of STAG1 gene. Chromosomal karyotyping and CNV-seq analysis did not reveal any chromosomal abnormalities. The WES result demonstrated a de novo NM_005862.3:c.1027-2A>G variant in STAG1 gene in the patient. This splicing variant was classified as likely pathogenic based on ACMG/AMP guidelines. Minigene array results showed that the variant could result in the appearance of premature termination codon.
Conclusion
Our study identified a novel pathogenic locus, c.1027-2A>G, associated with Intellectual developmental disorder, autosomal dominant 47 (MRD47).