Novel TMEM98, MFRP, PRSS56 variants in a large United States high hyperopia and nanophthalmos cohort.

Autor:	Prasov L; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA. lprasov@med.umich.edu.; Department of Human Genetics, University of Michigan, Ann Arbor, MI, 48109, USA. lprasov@med.umich.edu., Guan B; Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Ullah E; Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Archer SM; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA., Ayres BM; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA., Besirli CG; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA., Wiinikka-Buesser L; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA., Comer GM; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA., Del Monte MA; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA., Elner SG; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA., Garnai SJ; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA., Huryn LA; Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Johnson K; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA., Kamat SS; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA., Lieu P; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA., Mian SI; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA., Rygiel CA; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA., Serpen JY; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA.; Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.; Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA., Pawar HS; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA., Brooks BP; Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Moroi SE; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA.; Department of Ophthalmology and Visual Sciences, The Ohio State University, Columbus, OH, 43212, USA., Richards JE; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA., Hufnagel RB; Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA. Robert.hufnagel@nih.gov.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2020 Nov 17; Vol. 10 (1), pp. 19986. Date of Electronic Publication: 2020 Nov 17.
DOI:	10.1038/s41598-020-76725-8
Abstrakt:	Nanophthalmos is a rare condition defined by a small, structurally normal eye with resultant high hyperopia. While six genes have been implicated in this hereditary condition (MFRP, PRSS56, MYRF, TMEM98, CRB1,VMD2/BEST1), the relative contribution of these to nanophthalmos or to less severe high hyperopia (≥ + 5.50 spherical equivalent) has not been fully elucidated. We collected probands and families (n = 56) with high hyperopia or nanophthalmos (≤ 21.0 mm axial length). Of 53 families that passed quality control, plausible genetic diagnoses were identified in 10/53 (18.8%) by high-throughput panel or pooled exome sequencing. These include 1 TMEM98 family (1.9%), 5 MFRP families (9.4%), and 4 PRSS56 families (7.5%), with 4 additional families having single allelic hits in MFRP or PRSS56 (7.5%). A novel deleterious TMEM98 variant (NM_015544.3, c.602G>C, p.(Arg201Pro)) segregated with disease in 4 affected members of a family. Multiple novel missense and frameshift variants in MFRP and PRSS56 were identified. PRSS56 families were more likely to have choroidal folds than other solved families, while MFRP families were more likely to have retinal degeneration. Together, this study defines the prevalence of nanophthalmos gene variants in high hyperopia and nanophthalmos and indicates that a large fraction of cases remain outside of single gene coding sequences.
Databáze:	MEDLINE
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