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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.

SUBMITTER: Zhao B

PROVIDER: S-EPMC9437004 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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

Zhao Boxun B Madden Jill A JA Lin Jasmine J Berry Gerard T GT Wojcik Monica H MH Zhao Xuefang X Brand Harrison H Talkowski Michael M Lee Eunjung Alice EA Agrawal Pankaj B PB

European journal of human genetics : EJHG 20220630 9

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 ...[more]

PMID: 35768521

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Dataset Information

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

Publications

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

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