Autosomal dominant nanophthalmos and high hyperopia associated with a C-terminal frameshift variant in MYRF

Owen M. Siggs, Emmanuelle Souzeau, James Breen, Ayub Qassim, Tiger Zhou, Andrew Dubowsky, Jonathan B. Ruddle, Jamie E. Craig

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    Abstract

    Purpose: Nanophthalmos is a rare subtype of microphthalmia associated with high hyperopia and an increased risk of angle-closure glaucoma. We investigated the genetic cause of nanophthalmos and high hyperopia in an autosomal dominant kindred. Methods: A proband with short axial length, high hyperopia, and dextrocardia was subjected to exome sequencing. Human and rodent gene expression data sets were used to investigate the expression of relevant genes. Results: We identified a segregating heterozygous frameshift variant at the 3′ end of the penultimate exon of MYRF. Using Myc-MYRF chromatin immunoprecipitation data from rat oligodendrocytes, MYRF was found to bind immediately upstream of the transcriptional start site of Tmem98, a gene that itself has been implicated in autosomal dominant nanophthalmos. MYRF and TMEM98 were found to be expressed in the human retina, with a similar pattern of expression across several dissected human eye tissues. Conclusions: C-terminal variants in MYRF, which are expected to escape nonsense-mediated decay, represent a rare cause of autosomal dominant nanophthalmos with or without dextrocardia or congenital diaphragmatic hernia.

    Original languageEnglish
    Pages (from-to)527-534
    Number of pages8
    JournalMolecular Vision
    Volume25
    Publication statusPublished - 21 Sep 2019

    Bibliographical note

    Made available with a Creative Commons Attribution-NonCommercial-NoDerivatives License 3.0, or CC BY-NC-ND 3.0 (see http://creativecommons.org/licenses/by-nc-nd/3.0/ for license terms)

    Keywords

    • Ophthalmology
    • Nanophthalmos
    • microphthalmia
    • angle-closure glaucoma

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