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Novel disease loci
Short report
De novo variants in SUPT16H cause neurodevelopmental disorders associated with corpus callosum abnormalities
  1. Roya Bina1,
  2. Dena Matalon2,
  3. Brieana Fregeau1,
  4. Jacqueline Joani Tarsitano1,
  5. Ingvild Aukrust3,
  6. Gunnar Houge3,
  7. Renee Bend4,
  8. Hannah Warren4,
  9. Roger E Stevenson4,
  10. Kyra Eva Stuurman5,
  11. A James Barkovich6,
  12. Elliott H. Sherr1
  1. 1 Neurology, UCSF, San Francisco, California, USA
  2. 2 Pediatrics, Stanford University, Stanford, California, USA
  3. 3 Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway
  4. 4 Greenwood Genetic Center, Greenwood, South Carolina, USA
  5. 5 Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
  6. 6 Department of Radiology, UCSF, San Francisco, California, USA
  1. Correspondence to Dr Elliott H. Sherr, Neurology, UCSF, San Francisco, CA 94158, USA; Elliott.Sherr{at}ucsf.edu

Abstract

Introduction Whole-exome sequencing (WES) has identified de novo variants in chromatin remodelling genes in patients with neurodevelopmental disorders (NDD). We report on a novel genetic discovery in chromatin remodelling in patients with NDD who also have corpus callosum (CC) anomalies.

Objective To discover novel genes linked to both CC anomalies and NDD.

Methods Clinical WES was performed for evaluation of NDD, identifying five patients with de novo variants in SUPT16H, a subunit of the FACT (facilitates chromatin transcription) complex. The clinical phenotypes, genetic results and brain MRIs were obtained and systematically reviewed. In silico protein function predictions were assessed and allele frequencies in control populations were compared.

Results We identified four patients with de novo missense variants in SUPT16H and one patient with a de novo deletion including SUPT16H. These variants were not reported in the updated Genome Aggregation Database. When assayable, all protein products were predicted to be damaging. Symptoms included intellectual disability, autistic features, minor dysmorphic features and seizures. Anomalies of the CC were seen in all three patients with available brain imaging.

Conclusion Our findings implicate the gene SUPT16H in a novel disorder characterised by neurodevelopmental deficits and CC anomalies.

  • genetics
  • developmental
  • other neurology

https://doi.org/10.1136/jmedgenet-2019-106193

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    Footnotes

    • Presented at The results were initially presented at the Society for Neuroscience Annual Meeting, 2018.

    • Contributors RB, ES and BF contributed to the conception and design of the study. RB and BF contributed to data acquisition and interpretation of data for the work. GH, IA, RB, HW, RES and KES contributed by providing clinical data and editing of the manuscript. RB and JJT contributed to preparing the figures and original draft preparation. RB, ES and DM contributed to drafting the report and participated in final draft revisions. AJB contributed by evaluation of brain MRIs and preparation of the draft manuscript.

    • Funding This work was supported by a grant to ES from the National Institute of Neurological Disorders (NINDS) (5R01NS058721-10).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval This study was approved by site-specific institutional review boards, and informed consent was obtained from all individuals.

    • Provenance and peer review Not commissioned; externally peer reviewed.