A neurodevelopmental disorder caused by a novel de novo SVA insertion in exon 13 of the SRCAP gene.

Abstract

Pathogenic variants in the SRCAP (SNF2-related CREBBP activator protein) gene, which encodes a chromatin-remodeling ATPase, cause neurodevelopmental disorders including Floating Harbor syndrome (FLHS). Here, we report the discovery of a de novo transposon insertion in SRCAP exon 13 from trio genome sequencing in a 28-year-old female with failure to thrive, developmental delay, mood disorder and seizure disorder. The insertion was a full-length (~2.8 kb), antisense-oriented SVA insertion relative to the SRCAP transcript, bearing a 5' transduction and hallmarks of target-primed reverse transcription. The 20-bp 5' transduction allowed us to trace the source SVA element to an intron of a long non-coding RNA on chromosome 12, which is highly expressed in testis. RNA sequencing and qRT-PCR confirmed significant depletion of SRCAP expression and low-level exon skipping in the proband. This case highlights a novel disease-causing structural variant and the importance of transposon analysis in a clinical diagnostic setting.

• Authors: Boxun Zhao, Jill A Madden, Jasmine Lin, Gerard T Berry, Monica H Wojcik, Xuefang Zhao, Harrison Brand, Michael Talkowski, Eunjung Alice Lee, Pankaj B Agrawal
• Journal: European journal of human genetics : EJHG (Eur J Hum Genet) Vol. 30 Issue 9 Pg. 1083-1087 (09 2022) ISSN: 1476-5438 [Electronic] England
• PMID: 35768521 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2022. The Author(s), under exclusive licence to European Society of Human Genetics.

Chemical References

• Adenosine Triphosphatases
• SRCAP protein, human

Topics

• Abnormalities, Multiple (genetics)
• Adenosine Triphosphatases (genetics)
• Adult
• Craniofacial Abnormalities (genetics)
• Exons
• Female
• Heart Septal Defects, Ventricular (genetics)
• Humans
• Male
• Neurodevelopmental Disorders (diagnosis, genetics)