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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 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.

Item Type:	Article
Authors/Creators:	Siggs, OM and Awadalla, MS and Souzeau, E and Staffieri, SE and Kearns, LS and Laurie, K and Kuot, A and Qassim, A and Edwards, TL and Coote, MA and Mancel, E and Walland, MJ and Dondey, J and Galanopoulous, A and Casson, RJ and Mills, RA and MacArthur, DG and Ruddle, JB and Burdon, KP and Craig, JE
Keywords:	MFRP, MYRF, PRSS56, TMEM98, axial length, microphthalmia, nanophthalmos, posterior microphthalmos
Journal or Publication Title:	Clinical Genetics
Publisher:	Blackwell Munksgaard
ISSN:	0009-9163
DOI / ID Number:	10.1111/cge.13722
Copyright Information:	Copyright 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Related URLs:	Google Scholar: Burdon, KP UTAS Profile: Burdon, KP
Item Statistics:	View statistics for this item

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