1. The genetic and clinical landscape of nanophthalmos and posterior microphthalmos in an Australian cohort
- Author
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Daniel G. MacArthur, Abraham Kuot, Kate J. Laurie, Jamie E Craig, Lisa S. Kearns, Sandra E Staffieri, Robert J Casson, Erica Mancel, Joanne Dondey, Ayub Qassim, Thomas L Edwards, Jonathan B Ruddle, Mark J Walland, Emmanuelle Souzeau, Richard A. Mills, Anna Galanopoulous, Owen M. Siggs, Mona S Awadalla, Michael Coote, and Kathryn P. Burdon
- Subjects
Male ,0301 basic medicine ,Proband ,030105 genetics & heredity ,Biology ,Eye ,Microphthalmia ,Article ,Frameshift mutation ,Cohort Studies ,03 medical and health sciences ,Genetics ,medicine ,Humans ,Microphthalmos ,Frameshift Mutation ,Genetics (clinical) ,Exome sequencing ,Haplotype ,Australia ,Membrane Proteins ,Eye Diseases, Hereditary ,medicine.disease ,Genetic architecture ,Pedigree ,Hyperopia ,030104 developmental biology ,Cohort ,Female ,Serine Proteases ,Glaucoma, Angle-Closure ,Transcription Factors - Abstract
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 harboured 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.
- Published
- 2020
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