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 journalArticle

    Abstract

    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
    Volume97
    Issue number5
    Early online dateFeb 2020
    DOIs
    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

    Keywords

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

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  • Cite this

    Siggs, O. M., Awadalla, M., Souzeau, E., Staffieri, S., Kearns, L., 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., Burdon, K., & 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.13722