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Xiaohui Zhang, Ke Xu, Xiaolin Xu, Yang Li; TTR mutations and clinical characteristics of patients with vitreous amyloidosis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):405.
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© ARVO (1962-2015); The Authors (2016-present)
Investigate the transthyretin (TTR) mutations and clinical characteristics of patients with vitreous amyloidosis.
The study was approved by the Beijing Tongren Hospital Ethics Committee and followed the tenets of the Declaration of Helsinki. Ten cases of suspected vitreous amyloidosis were recruited from the ophthalmologic clinic of Beijing Tongren Hospital from 2011 to 2017. The patients and their relatives underwent detailed ophthalmologic examination. After obtaining informed consent, genomic DNA was extracted from peripheral blood samples of patients and their available family members. The 4 exons of TTR were amplified by PCR, followed by Sanger sequencing. The pathogenicity of gene variants were predicted by Polyphen2, MutationTaster, SIFT, and PMut. The allele frequency of gene variants was searched in the 1000 Genome, EVS, and ExAC database. Co-segregation analysis was performed in family members. The vitreous specimen of 5 patients obtained during vitrectomy was stained with HE and Congo red.
Six reported missense mutations of TTR, including p.V30A, p.K35N, p.L55R, p.Y69H, p.G83R, and p.Y114C, were identified in 8 patients. The mutations are located in the beta-strand and beta-hairpin domain of TTR. The average onset age of 8 patients was 41.9±8.9 years. All patients showed dense grayish white cord or agglomerate opacity in the vitreous. HE staining of vitreous specimens in 5 patients showed that there was no structural substance. Congo red staining was positive in 1 patient. Six of 8 patients showed combined hearing system, autonomic nervous system or peripheral nervous system abnormalities.
The p.G83R mutation is a mutation hotspot in Chinese patients with vitreous amyloidosis. The β-strand C is the protein region where common TTR mutations are located. Mutation screening of TTR is easier, quicker, and more sensitive than pathological test for the diagnosis of vitreous amyloidosis.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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