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Marina Ogawa, Yoshihiko Usui, Naoyuki Yamakawa, Kazuhiko Umazume, Kinya Tsubota, Rei Nemoto, Hiroshi Goto; Genetic analysis of IgG4-related ophthalmic disease using next-generation sequencing. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4324. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Comprehensive analysis of genetic alterations in IgG4-related ophthalmic disease (IgG4-ROD) may play an important role in discovering novel biomarkers and establishing treatments. However, the analytical method is still in the development stage. We reported our analysis of genetic alterations in IgG4-ROD using next-generation sequencing (NGS) in ARVO 2017. In the previous report, we compared genetic alterations of the biopsy specimen with those from peripheral blood. In this presentation, we report our analysis of genetic alterations using oral mucosa as control, instead of peripheral blood. We take the potential masking of gene abnormality in peripheral blood into consideration.
This study included 9 patients who were diagnosed with IgG4-ROD at Tokyo Medical University Hospital. These patients comprised 4 males and 5 females, with an average age of 62.9 years. The average serum IgG4 level was 706.8 mg/dl. Genome DNA was extracted from biopsy specimen obtained from lacrimal gland for the diagnostic purpose and oral mucosa, and analyzed using a MiSeq Sequencing System with TruSight One sequencing panel (Illumina), which targets 4,813 genes. Variant Studio software was used to analyze the data. In addition, we measured mutant protein levels in the serum of patient by ELISA.
We detected 9,643 genes from biopsy specimen and 9,736 genes from oral mucosa using NGS. Alterations in FMN2, GLTSCR1, INF2 were found in all samples of the 9 patients, while irregularities in RPGR, PRDM9, TRIOBP were observed in 8 patients. Serum levels of TRIOBP and INF2 in IgG4-ROD were significantly lower than that in healthy controls.
Using oral mucosa as controls, we identified other novel genetic alterations in IgG4-ROD. This new finding may contribute to establish novel biomarkers and treatments in the future.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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