Abstract
High myopia (HM) is a leading cause of visual impairment in the world. To expand the genotypic and phenotypic spectra of HM in the Chinese population, we investigated genetic variations in a cohort of 113 families with nonsyndromic early-onset high myopia from northwestern China by whole-exome sequencing, with focus on 17 known genes. Sixteen potentially pathogenic variants predicted to affect protein function in eight of seventeen causative genes for HM in fifteen (13.3%) families were revealed, including seven novel variants, c.767 + 1G > A in ARR3, c.3214C > A/p.H1072N, and c.2195C > T/p.A732V in ZNF644, c.1270G > T/p.V424L in CPSF1, c.1918G > C/p.G640R and c.2786T > G/p.V929G in XYLT1, c.601G > C/p.E201Q in P4HA2; six rare variants, c.799G > A/p.E267K in NDUFAF7, c.1144C > T/p.R382W in TNFRSF21, c.1100C > T/p.P367L in ZNF644, c.3980C > T/p.S1327L in CPSF1, c.145G > A/p.E49K and c.325G > T/p.G109W in SLC39A5; and three known variants, c.2014A > G/p.S672G and c.3261A > C/p.E1087D in ZNF644, c.605C > T/p.P202L in TNFRSF21. Ten of them were co-segregated with HM. The mean (± SD) examination age of these 15 probands was 14.7 (± 11.61) years. The median spherical equivalent was − 9.50 D (IQ − 8.75 ~ − 12.00) for the right eye and − 11.25 D (IQ − 9.25 ~ − 14.13) for the left eye. The median axial length was 26.67 mm (IQ 25.83 ~ 27.13) for the right eye and 26.25 mm (IQ 25.97 ~ 27.32) for the left eye. These newly identified genetic variations not only broaden the genetic and clinical spectra, but also offer convincing evidence that the genes ARR3, NDUFAF7, TNFRSF21, and ZNF644 contribute to hereditable HM. This work improves further understanding of molecular mechanism of HM.
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Data availability
All data generated or analysed during this study are included in this published article. The raw WES sequencing and blood samples of the 113 patients in the current study are not openly available due to ethical concerns, but are available from the corresponding author on reasonable request.
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Acknowledgements
This study was supported by the National Natural Science Foundation of China (82060182, 82125007), the Ningxia Natural Science Foundation (2021AAC03301) and Ningxia Key R&D program of China (2019BEG03016).
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WZ and ZJ designed the work and revised the manuscript; MY, YQ, BC, LM, ZM, and YL performed the experiments; MY, YQ, and BC analyzed and interpreted data; MY and YM wrote the manuscript. All authors approved the final manuscript.
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Ye, M., Ma, Y., Qin, YX. et al. Mutational investigation of 17 causative genes in a cohort of 113 families with nonsyndromic early-onset high myopia in northwestern China. Mol Genet Genomics 298, 669–682 (2023). https://doi.org/10.1007/s00438-023-02003-7
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DOI: https://doi.org/10.1007/s00438-023-02003-7