Rxivist logo

Duplications at 19q13.33 in patients with neurodevelopmental disorders

By Eduardo PĂ©rez-Palma, Elmo Saarentaus, Joris Andrieux, Marie Ravoet, Giancarlo V De Ferrari, Peter Nuernberg, Bertrand Isidor, Bernd A. Neubauer, Dennis Lal

Posted 25 Apr 2017
bioRxiv DOI: 10.1101/130377 (published DOI: 10.1212/nxg.0000000000000210)

OBJECTIVE: After recent publication of the first patients with disease associated missense variants in GRIN2D, we evaluate the effect of copy number variation (CNV) overlapping this gene towards the presentation of neurodevelopmental disorders. METHODS: We explored ClinVar (N CNV = 41,398) and DECIPHER (N CNV = 30,222) clinical databases of genomic variations for patients with copy number changes overlapping the GRIN2D gene at the 19q13.33 locus and evaluated their respective phenotype alongside their frequency, gene content and expression with publicly available reference databases. RESULTS: We identified 13 patients with microduplications at the 19q13.33 locus. The majority of CNVs arose de novo and comparable CNVs are not present in control databases. All patients were reported to have neurodevelopmental disorders and dysmorphic features as the most common clinical phenotype (N= 10/13), followed by seizures (N= 6/13) and intellectual disability (N= 5/13). All duplications shared a consensus region of 405 kb overlapping 13 genes. After screening for duplication tolerance in control populations, positive gene brain expression and gene dosage sensitivity analysis, we highlight four genes for future evaluation: CARD8, C19orf68, KDELR1 and GRIN2D, which are promising candidates for disease causality. Further, investigation of the literature especially supports GRIN2D as the best candidate gene. CONCLUSIONS: Our study presents dup19q13.33 as novel duplication syndrome locus associated with neurodevelopmental disorders. CARD8, C19orf68, KDELR1 and GRIN2D are promising candidates for functional follow up.

Download data

  • Downloaded 367 times
  • Download rankings, all-time:
    • Site-wide: 51,299 out of 101,077
    • In genetics: 2,853 out of 5,028
  • Year to date:
    • Site-wide: 90,633 out of 101,077
  • Since beginning of last month:
    • Site-wide: 88,125 out of 101,077

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News

  • 20 Oct 2020: Support for sorting preprints using Twitter activity has been removed, at least temporarily, until a new source of social media activity data becomes available.
  • 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
  • 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
  • 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
  • 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
  • 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
  • 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
  • 22 Jan 2019: Nature just published an article about Rxivist and our data.
  • 13 Jan 2019: The Rxivist preprint is live!