July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Whole-exome sequencing identifies a novel homozygous missense variant in REEP6 gene in a retinitis pigmentosa patient complicated with macular hole
Author Affiliations & Notes
  • Bo Lei
    Ophthalmology, Henan Eye Institute, People's Hospital of Henan , Zhengzhou, China
  • Footnotes
    Commercial Relationships   Bo Lei, None
  • Footnotes
    Support  National Natural Science Foundation of China grants(81271033,81470621)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4489. doi:
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    • Get Citation

      Bo Lei; Whole-exome sequencing identifies a novel homozygous missense variant in REEP6 gene in a retinitis pigmentosa patient complicated with macular hole. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4489.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : REEP6 plays an essential role in maintaining cGMP homeostasis though facilitating the stability and trafficking of guanylate cyclase. It is also important in maintaining ER and mitochondrial homeostasis. This study was to identify the underlying gene defect leading to retinitis pigmentosa in a Chinese patient.

Methods : A 55-year-old Asian male proband complained night blindness and decrease of vision acuity for 20 years. Ophthalmic examinations including fundus photography, spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (AF), infrared reflectance (IR) and full-field electroretinogram (fERG) were conducted. Blood samples from the proband, his consanguineous parents, son and wife were collected. Whole-exome sequencing (WES) followed by Sanger validation was performed.

Results : The visual acuity of the proband was light perception in the right eye and 0.02 in the left eye. Fundus showed bone-spicule deposits and the ERG responses were non-recordable. Outer nuclear layer and ellipsoid zone loss outside the fovea was observed. Bilateral macular hole (MH) and epiretinal membranes (ERMs) were evident. WES data analyses identified 2 presumably homozygous variants in REEP6 and NPHP4 respectively. Since the patient did not exhibit kidney and mental disorders, the causative variant was most likely attributed to the novel missense mutation in exome 3 of REEP6 (c.268G>C, p.V90L, NM_138393.1), which encoded a transmembrane domain of the reep6 protein. With a frequency of 0.01158 in the Asian population (ExAC), this variation previously has not been reported. Bioinformatics analysis with Mutation Taster, SIFT and PolyPhen2 indicated the mutation was harmful. The parents and the son of the proband, who did not present the above signs, were heterozygous of the variant, while his wife did not have such a variant.

Conclusions : A novel homozygous missense variant c.268G>C, p.V90L in REEP6 in a retinitis pigmentosa 77 patient originating from a consanguineous Chinese couple may be disease-causing. Our finding expanded the mutation spectrum of REEP6 in RP. In addition, not only loss of photoreceptor layer but also involvement of vitreoretinal interface, which caused MH, were observed in this case. Whether the bilateral MH was related with the variant remains unknown.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.


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