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

Owen M Siggs, Mona Awadalla, Emmanuelle Souzeau, Sandra Staffieri, Lisa Kearns, Kate Laurie, Abraham Kuot, Ayub Qassim, Thomas L Edwards, Michael A. Coote, Erica Mancel, Mark J. Walland, Joanne Dondey, Anna Galanopoulous, Robert J Casson, Richard A Mills, Daniel G MacArthur, Jonathan Ruddle, Kathryn Burdon, Jamie E Craig

    Research output: Contribution to journalArticlepeer-review

    5 Citations (Scopus)


    Nanophthalmos and posterior microphthalmos are ocular abnormalities in which botheyes are abnormally small, and typically associated with extreme hyperopia. We rec-ruited 40 individuals from 13 kindreds with nanophthalmos or posteriormicrophthalmos, with 12 probands subjected to exome sequencing. Nine probands(69.2%) were assigned a genetic diagnosis, with variants inMYRF,TMEM98,MFRP,andPRSS56. Two of fourPRSS56families harbored the previously describedc.1066dupC variant implicated in over half of all reportedPRSS56kindreds, withdifferent surrounding haplotypes in each family suggesting a mutational hotspot. Indi-viduals with a genetic diagnosis had shorter mean axial lengths and higher hyperopiathan those without, with recessive forms associated with the most extreme pheno-types. These findings detail the genetic architecture of nanophthalmos and posteriormicrophthalmos in a cohort of predominantly European ancestry, their relative clinicalphenotypes, and highlight the shared genetic architecture of rare and common disor-ders of refractive error.
    Original languageEnglish
    Pages (from-to)764-769
    Number of pages6
    JournalClinical Genetics
    Issue number5
    Early online dateFeb 2020
    Publication statusPublished - May 2020

    Bibliographical note

    © 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 policy


    • Axial Length
    • MRFP
    • Microphthalmia
    • MYRF
    • Nanophthalmos
    • Posterier Microphthalmos
    • PRSS56
    • TMEM98
    • microphthalmia
    • axial length
    • posterior microphthalmos
    • MFRP
    • nanophthalmos


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