The genetic and clinical landscape of nanophthalmos and posterior microphthalmos in an Australian cohort

dc.contributor.authorSiggs, Owen Men_US
dc.contributor.authorAwadalla, Mona Sen_US
dc.contributor.authorSouzeau, Emmanuelleen_US
dc.contributor.authorStaffieri, Sandra Een_US
dc.contributor.authorKearns, Lisa Aen_US
dc.contributor.authorLaurie, Kateen_US
dc.contributor.authorKuot, Abrahamen_US
dc.contributor.authorQassim, Ayuben_US
dc.contributor.authorEdwards, Thomas Len_US
dc.contributor.authorCoote, Michael Aen_US
dc.contributor.authorMancel, Ericaen_US
dc.contributor.authorWalland, Mark Jen_US
dc.contributor.authorDondey, Joanneen_US
dc.contributor.authorGalanopoulous, Annaen_US
dc.contributor.authorCasson, Robert Jen_US
dc.contributor.authorMills, Richard Aen_US
dc.contributor.authorMacArthur, Daniel Gen_US
dc.contributor.authorRuddle, Jonathan Ben_US
dc.contributor.authorBurdon, Kathryn Pen_US
dc.contributor.authorCraig, Jamie Een_US
dc.date.accessioned2020-05-27T04:44:08Z
dc.date.available2020-05-27T04:44:08Z
dc.date.issued2020-05
dc.description© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. This author accepted manuscript is made available following 12 month embargo from date of publication (February 2020) in accordance with the publisher’s archiving policyen_US
dc.description.abstractNanophthalmos and posterior microphthalmos are ocular abnormalities in which both eyes are abnormally small, and typically associated with extreme hyperopia. We recruited 40 individuals from 13 kindreds with nanophthalmos or posterior microphthalmos, with 12 probands subjected to exome sequencing. Nine probands (69.2%) were assigned a genetic diagnosis, with variants in MYRF , TMEM98 , MFRP , and PRSS56 . Two of four PRSS56 families harbored the previously described c.1066dupC variant implicated in over half of all reported PRSS56 kindreds, with different surrounding haplotypes in each family suggesting a mutational hotspot. Individuals with a genetic diagnosis had shorter mean axial lengths and higher hyperopia than those without, with recessive forms associated with the most extreme phenotypes. These findings detail the genetic architecture of nanophthalmos and posterior microphthalmos in a cohort of predominantly European ancestry, their relative clinical phenotypes, and highlight the shared genetic architecture of rare and common disorders of refractive error.en_US
dc.identifier.citationSiggs, O. M., Awadalla, M. S., Souzeau, E., Staffieri, S. E., Kearns, L. S., Laurie, K., Kuot, A., Qassim, A., Edwards, T. L., Coote, M. A., Mancel, E., Walland, M. J., Dondey, J., Galanopoulous, A., Casson, R. J., Mills, R. A., MacArthur, D. G., Ruddle, J. B., Burdon, K. P., & Craig, J. E. (2020). The genetic and clinical landscape of nanophthalmos and posterior microphthalmos in an Australian cohort. Clinical Genetics, 97(5), 764–769. https://doi.org/10.1111/cge.13722en_US
dc.identifier.doihttps://doi.org/10.1111/cge.13722en_US
dc.identifier.issn1399-0004
dc.identifier.urihttp://hdl.handle.net/2328/39368
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relationhttp://purl.org/au-research/grants/NHMRC/1107098en_US
dc.relation.grantnumberNHMRC/1107098en_US
dc.rights© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltden_US
dc.rights.holderJohn Wiley & Sons A/Sen_US
dc.subjectaxial lengthen_US
dc.subjectMFRPen_US
dc.subjectmicrophthalmiaen_US
dc.subjectMYRF nanophthalmosen_US
dc.subjectnanophthalmosen_US
dc.subjectposterior microphthalmosen_US
dc.subjectPRSS56en_US
dc.subjectTMEM98en_US
dc.titleThe genetic and clinical landscape of nanophthalmos and posterior microphthalmos in an Australian cohorten_US
dc.typeArticleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Siggs_Genetic_AM2020.pdf
Size:
1.01 MB
Format:
Adobe Portable Document Format
Description:
Author version
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.84 KB
Format:
Item-specific license agreed upon to submission
Description: