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


Siggs, OM and Awadalla, MS and Souzeau, E and Staffieri, SE and Kearns, LS and Laurie, K and Kuot, A and Qassim, A and Edwards, TL and Coote, MA and Mancel, E and Walland, MJ and Dondey, J and Galanopoulous, A and Casson, RJ and Mills, RA and MacArthur, DG and Ruddle, JB and Burdon, KP and Craig, JE, The genetic and clinical landscape of nanophthalmos and posterior microphthalmos in an Australian cohort, Clinical Genetics, 97, (5) pp. 764-769. ISSN 0009-9163 (2020) [Refereed Article]

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Copyright 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

DOI: doi:10.1111/cge.13722


Nanophthalmos 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.

Item Details

Item Type:Refereed Article
Keywords:MFRP, MYRF, PRSS56, TMEM98, axial length, microphthalmia, nanophthalmos, posterior microphthalmos
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
ID Code:139514
Year Published:2020
Web of Science® Times Cited:7
Deposited By:Menzies Institute for Medical Research
Deposited On:2020-06-18
Last Modified:2020-07-15
Downloads:7 View Download Statistics

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