Autosomal recessive optic neuropathies (IONs) are extremely rare disorders affecting retinal ganglion cells and the nervous system. RTN4IP1 has recently been identified as the third known gene associated with the autosomal recessive ION optic atrophy 10 (OPA10). Patients with RTN4IP1 mutations show early-onset optic neuropathy that can be followed by additional neurological symptoms such as seizures, ataxia, mental retardation, or even severe encephalopathy. Here, we report two siblings from a Chinese family who presented with early-onset optic neuropathy, epilepsy, and mild intellectual disability. Using whole exome sequencing combined with Sanger sequencing, we identified novel compound heterozygous RTN4IP1 mutations (c.646G > A, p.G216R and c.1162C > T, p.R388X) which both co-segregated with the disease phenotype and were predicted to be disease-causing by prediction software. An in vitro functional study in urine cells obtained from one of the patients revealed low expression of the RTN4IP1 protein. Our results identify novel compound heterozygous mutations in RTN4IP1 which are associated with OPA10, highlighting the frequency of RTN4IP1 mutations in human autosomal recessive IONs. To our knowledge, this is the first report of RTN4IP1 carriers from China.
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We thank Sarah Williams, PhD, from Liwen Bianji, Edanz Group China (www.liwenbianji.cn), for editing the English text of a draft of this manuscript.
This work was supported by the National Natural Science Foundation of China (grant nos. 81701133, 81322017, 81771230, and U1505222), the Joint Funds for the Innovation of Science and Technology, Fujian Province (2017Y9087), and the National Key Clinical Specialty Discipline Construction Program and Key Clinical Specialty Discipline Construction Program of Fujian.
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Zou, X., Guo, X., Su, H. et al. Whole Exome Sequencing Identifies Two Novel Mutations in the Reticulon 4–Interacting Protein 1 Gene in a Chinese Family with Autosomal Recessive Optic Neuropathies. J Mol Neurosci 68, 640–646 (2019). https://doi.org/10.1007/s12031-019-01319-7
- Inherited optic neuropathies
- Optic atrophy