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Invest Ophthalmol Vis Sci. 2017 Aug 1;58(10):4182-4192. doi: 10.1167/iovs.16-20941.

A Novel Potentially Causative Variant of NDUFAF7 Revealed by Mutation Screening in a Chinese Family With Pathologic Myopia.

Wang B1,2, Liu Y3, Chen S1,2, Wu Y1,2, Lin S1,2, Duan Y1,2, Zheng K1,2, Zhang L1, Gu X1, Hong W1, Shao H1, Zeng X1, Sun B3, Duan S1,2.

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Laboratory of Medical Genetics, Shenzhen Research Institute of Population and Family Planning, Shenzhen, China.
Shenzhen Center for Birth Defect Research and Prevention, Shenzhen, China.
Department of Ophthalmology, The People's Hospital of Wenshan Prefecture, Wenshan Zhuang-Miao Autonomous Prefecture, China.



Pathologic myopia described as myopia accompanied by severe deformation of the eye besides excessive elongation of eye, is usually a genetic heterogeneous disorder characterized by extreme, familial, early-onset vision loss. However, the exact pathogenesis of pathologic myopia remains unclear. In this study, we screened a Han Chinese family with pathologic myopia to identify the causative mutation and explore the possible pathogenic mechanism based on evaluation of the biological functions of the mutation.


We identified the mutations in a family with pathologic myopia by single nucleotide polymorphism array combined with short tandem repeat microsatellite marker analysis and exome sequencing. Mutations were validated among family members by direct Sanger sequencing. The subcellular localization of the protein variant was investigated by immunofluorescence, and the stability of the mutant protein was determined by immunoblotting. Intracellular levels of adenosine triphosphate and reactive oxygen species and complex I activity were measured by traditional biochemical methods to determine the functional role of the disease-associated mutation.


The novel missense mutation: c.798C>G (p.Asp266Glu) in NDUFAF7, cosegregated with the disease and the resulting amino acid substitution affected a highly conserved residue in its protein. The mutation D266E in NDUFAF7 impaired complex I activity, which resulted in decreased ATP levels in cultured cells.


We propose that the heterozygous mutation (c.798C>G) in NDUFAF7 may contribute to the pathogenesis of pathologic myopia, possibly by interfering with the phototransduction cascade. Mitochondrial dysfunction during eye development may lead to pathologic myopia.

[Indexed for MEDLINE]

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