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. 2022 Apr 11;23(8):4233.
doi: 10.3390/ijms23084233.

Next-Generation Sequencing Screening of 43 Families with Non-Syndromic Early-Onset High Myopia: A Clinical and Genetic Study

Eva González-Iglesias  1 , Ana López-Vázquez  2 , Susana Noval  2 , María Nieves-Moreno  2 , María Granados-Fernández  2 , Natalia Arruti  2 , Irene Rosa-Pérez  2 , Marta Pacio-Míguez  3   4 , Victoria E F Montaño  1   3 , Patricia Rodríguez-Solana  1 , Angela Del Pozo  3   5 , Fernando Santos-Simarro  3   6 , Elena Vallespín  1   3
Affiliations

Next-Generation Sequencing Screening of 43 Families with Non-Syndromic Early-Onset High Myopia: A Clinical and Genetic Study

Eva González-Iglesias et al. Int J Mol Sci. .

Abstract

Early-onset high myopia (EoHM) is a disease that causes a spherical refraction error of ≥-6 diopters before 10 years of age, with potential multiple ocular complications. In this article, we report a clinical and genetic study of 43 families with EoHM recruited in our center. A complete ophthalmological evaluation was performed, and a sample of peripheral blood was obtained from proband and family members. DNA was analyzed using a customized next-generation sequencing panel that included 419 genes related to ophthalmological disorders with a suspected genetic cause, and genes related to EoHM pathogenesis. We detected pathogenic and likely pathogenic variants in 23.9% of the families and detected variants of unknown significance in 76.1%. Of these, 5.7% were found in genes related to non-syndromic EoHM, 48.6% in genes associated with inherited retinal dystrophies that can include a syndromic phenotype, and 45.7% in genes that are not directly related to EoHM or retinal dystrophy. We found no candidate genes in 23% of the patients, which suggests that further studies are needed. We propose a systematic genetic analysis for patients with EoHM because it helps with follow-up, prognosis and genetic counseling.

Keywords: early-onset high myopia; next-generation sequencing; ophthalmogenetics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Posterior staphyloma. Right and left eyes. Optos (Marlborough, MA, USA).
Figure 2
Figure 2
Diffuse chorioretinal atrophy. Right and left eyes. Optos (Marlborough, MA, USA).
Figure 3
Figure 3
Optic nerve OCT with peripapillary atrophy, from left to right, OD and OS. Patient from family OFT-0047.
Figure 4
Figure 4
Macular OCT with central staphyloma, from left to right OD and OS. Patient from family OFT-0047.
Figure 5
Figure 5
Representation of genes with pathogenic and likely pathogenic variants and their proportion.
Figure 6
Figure 6
Representation of genes with variants of unknown significance and their proportion.
Figure 7
Figure 7
Diagnostic algorithm for early-onset high myopia. EoHM, early-onset high myopia; CNVs, copy number variants; ACMG, American College of Medical Genetics; NGS, next-generation sequencing; WES, whole exome sequencing; WGS, whole genome sequencing.
See this image and copyright information in PMC

References

    1. Aránguez-Cortés C., Cortés-Orduña I., del-Río-Fernández S., Donate-López J., Franco-Iglesias G., García-Sáenz S., Gil-Ruiz R., Isasi-Saseta M., Martín-Justicia A., Martín-Hernández E., et al. Manual de Refracción para Residentes de Oftalmología. 2nd ed. Essilor; Madrid, Spain: 2007.
    1. Durajczyk M., Grudzińska E., Obszańska A., Modrzejewska M. Myopia. Definition and classification according to the latest knowledge. Ophtha Therapy. 2021;4:226–231. doi: 10.24292/01.OT.021221. - DOI
    1. Holden B.A., Fricke T.R., Wilson D.A., Jong M., Naidoo K.S., Sankaridurg P., Wong T.Y., Naduvilath T., Resnikoff S. Global Prevalence of Myopia and High Myopia and Temporal Trends from 2000 through 2050. Ophthalmology. 2016;123:1036–1042. doi: 10.1016/j.ophtha.2016.01.006. - DOI - PubMed
    1. Zhou L., Xiao X., Li S., Jia X., Zhang Q. Frequent mutations of RetNet genes in eoHM: Further confirmation in 325 probands and comparison with late-onset high myopia based on exome sequencing. Exp. Eye Res. 2018;171:76–91. doi: 10.1016/j.exer.2018.02.007. - DOI - PubMed
    1. Alvarez-Peregrina C.C., Sanchez-Tena M.A.M.A., Martinez-Perez C.C., Villa-Collar C.C. Prevalence and Risk Factors of Myopia in Spain. J. Ophthalmol. 2019;2019:1–7. doi: 10.1155/2019/3419576. - DOI - PMC - PubMed

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