The genetic and clinical landscape of nanophthalmos in an Australian cohort
Owen M Siggs,
Mona S Awadalla,
Lisa S Kearns,
Thomas L Edwards,
Michael A Coote,
Mark J Walland,
Robert J Casson,
Richard A Mills,
Daniel G. MacArthur,
Jonathan B Ruddle,
Kathryn P Burdon,
Jamie E Craig
Posted 04 Dec 2019
medRxiv DOI: 10.1101/19013599
Posted 04 Dec 2019
PurposeRefractive error is caused by a disparity between the axial length and focusing power of the eye. Nanophthalmos is a rare ocular abnormality in which both eyes are abnormally small, typically causing extreme hyperopic refractive error, and associated with an increased risk of angle-closure glaucoma. MethodsA cohort of 40 individuals from 13 unrelated nanophthalmos kindreds were recruited, with 11 probands subjected to exome sequencing. ResultsNine probands (69.2%) were assigned a genetic diagnosis, with variants in PRSS56 (4), MFRP (3), and previously reported variants in TMEM98 (1) and MYRF (1). Two of the four PRSS56 probands harboured the previously described c.1066dupC frameshift variant implicated in over half of all reported PRSS56 kindreds, with surrounding haplotypes distinct from each other, and from a previously reported Tunisian c.1066dupC haplotype. Individuals with a genetic diagnosis had shorter mean axial lengths (P=7.22x10-9) and more extreme hyperopia (P=0.0005) than those without a genetic diagnosis, with recessive forms associated with the shortest axial lengths and highest hyperopia. All individuals with an axial length below 18 mm in their smaller eye (17/17) were assigned a genetic diagnosis. ConclusionsThese findings detail the genetic architecture of nanophthalmos in an Australian cohort of predominantly European ancestry, their relative clinical phenotypes, and highlight the shared genetic architecture of rare and common disorders of refractive error.
- Downloaded 375 times
- Download rankings, all-time:
- Site-wide: 137,409
- In genetic and genomic medicine: 953
- Year to date:
- Site-wide: 128,860
- Since beginning of last month:
- Site-wide: 128,308
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!