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

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Siggs, Owen M
Awadalla, Mona S
Souzeau, Emmanuelle
Staffieri, Sandra E
Kearns, Lisa A
Laurie, Kate
Kuot, Abraham
Qassim, Ayub
Edwards, Thomas L
Coote, Michael A
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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.
© 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, MFRP, microphthalmia, MYRF nanophthalmos, nanophthalmos, posterior microphthalmos, PRSS56, TMEM98
Siggs, 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.