RGD Reference Report - Variants in myelin regulatory factor (MYRF) cause autosomal dominant and syndromic nanophthalmos in humans and retinal degeneration in mice. - Rat Genome Database

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Variants in myelin regulatory factor (MYRF) cause autosomal dominant and syndromic nanophthalmos in humans and retinal degeneration in mice.

Authors: Garnai, Sarah J  Brinkmeier, Michelle L  Emery, Ben  Aleman, Tomas S  Pyle, Louise C  Veleva-Rotse, Biliana  Sisk, Robert A  Rozsa, Frank W  Ozel, Ayse Bilge  Li, Jun Z  Moroi, Sayoko E  Archer, Steven M  Lin, Cheng-Mao  Sheskey, Sarah  Wiinikka-Buesser, Laurel  Eadie, James  Urquhart, Jill E  Black, Graeme C M  Othman, Mohammad I  Boehnke, Michael  Sullivan, Scot A  Skuta, Gregory L  Pawar, Hemant S  Katz, Alexander E  Huryn, Laryssa A  Hufnagel, Robert B  Genomic Ascertainment Cohort,   Camper, Sally A  Richards, Julia E  Prasov, Lev 
Citation: Garnai SJ, etal., PLoS Genet. 2019 May 2;15(5):e1008130. doi: 10.1371/journal.pgen.1008130. eCollection 2019 May.
RGD ID: 197810045
Pubmed: PMID:31048900   (View Abstract at PubMed)
PMCID: PMC6527243   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pgen.1008130   (Journal Full-text)

Nanophthalmos is a rare, potentially devastating eye condition characterized by small eyes with relatively normal anatomy, a high hyperopic refractive error, and frequent association with angle closure glaucoma and vision loss. The condition constitutes the extreme of hyperopia or farsightedness, a common refractive error that is associated with strabismus and amblyopia in children. NNO1 was the first mapped nanophthalmos locus. We used combined pooled exome sequencing and strong linkage data in the large family used to map this locus to identify a canonical splice site alteration upstream of the last exon of the gene encoding myelin regulatory factor (MYRF c.3376-1G>A), a membrane bound transcription factor that undergoes autoproteolytic cleavage for nuclear localization. This variant produced a stable RNA transcript, leading to a frameshift mutation p.Gly1126Valfs*31 in the C-terminus of the protein. In addition, we identified an early truncating MYRF frameshift mutation, c.769dupC (p.S264QfsX74), in a patient with extreme axial hyperopia and syndromic features. Myrf conditional knockout mice (CKO) developed depigmentation of the retinal pigment epithelium (RPE) and retinal degeneration supporting a role of this gene in retinal and RPE development. Furthermore, we demonstrated the reduced expression of Tmem98, another known nanophthalmos gene, in Myrf CKO mice, and the physical interaction of MYRF with TMEM98. Our study establishes MYRF as a nanophthalmos gene and uncovers a new pathway for eye growth and development.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MYRFHumannanophthalmos  IAGP DNA:mutations:cds:RGD 
MyrfRatnanophthalmos  ISOMYRF (Homo sapiens)DNA:mutations:cds:RGD 
MyrfMousenanophthalmos  ISOMYRF (Homo sapiens)DNA:mutations:cds:RGD 
MYRFHumanretinal degeneration  ISOMyrf (Mus musculus) RGD 
MyrfRatretinal degeneration  ISOMyrf (Mus musculus) RGD 
MyrfMouseretinal degeneration  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Myrf  (myelin regulatory factor)

Genes (Mus musculus)
Myrf  (myelin regulatory factor)

Genes (Homo sapiens)
MYRF  (myelin regulatory factor)


Additional Information