The genetic and clinical landscape of nanophthalmos and posterior microphthalmos in an Australian cohort
journal contributionposted on 2023-05-20, 15:18 authored by Siggs, OM, Awadalla, MS, Souzeau, E, Staffieri, SE, Kearns, LS, Laurie, K, Kuot, A, Qassim, A, Edwards, TL, Coote, MA, Mancel, E, Walland, MJ, Dondey, J, Galanopoulous, A, Casson, RJ, Mills, RA, MacArthur, DG, Ruddle, JB, Kathryn BurdonKathryn Burdon, Craig, JE
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.
Publication titleClinical Genetics
Department/SchoolMenzies Institute for Medical Research
Place of publication35 Norre Sogade, Po Box 2148, Copenhagen, Denmark, Dk-1016
Rights statementCopyright 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.