Pathogenic variants in SMARCA5, a chromatin remodeler, cause a range of syndromic neurodevelopmental features
Naihua N Gong,
Hagit Baris Feldman,
Maria J. Guillen Sacoto,
Michael E. March,
Elizabeth J Bhoj,
Małgorzata J.M. Nowaczyk,
Julian A Martinez,
Eva MC Schwaibold,
Lynn S Pais,
Susan M. White,
Matthew S. Kayser,
Tiong Yang Tan,
Matthew A Deardorff,
Posted 28 Oct 2020
medRxiv DOI: 10.1101/2020.10.26.20217109
Posted 28 Oct 2020
Intellectual disability (ID) encompasses a wide spectrum of neurodevelopmental disorders, with many linked genetic loci. However, the underlying molecular mechanism for over 50% of the patients remains elusive. We describe mutations in SMARCA5, encoding the ATPase motor of the ISWI chromatin remodeler, as a cause of a novel neurodevelopmental disorder, identifying twelve individuals with de novo or dominantly segregating rare heterozygous variants. Accompanying phenotypes include mild developmental delay, frequent postnatal short stature, and microcephaly, and recurrent dysmorphic features. Loss of function of the SMARCA5 Drosophila ortholog Iswi led to smaller body size, reduced dendrite complexity, and tiling defects in larvae. In adult flies, Iswi neural knockdown caused decreased brain size, aberrant mushroom body morphology and abnormal locomotor function. Iswi loss of function was rescued by wild-type but not mutant SMARCA5. Our results demonstrate that SMARCA5 pathogenic variants cause a neurodevelopmental syndrome with mild facial dysmorphia.
- Downloaded 194 times
- Download rankings, all-time:
- Site-wide: 108,077
- In genetic and genomic medicine: 469
- Year to date:
- Site-wide: 30,275
- Since beginning of last month:
- Site-wide: 25,793
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 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!