Authors: Zhang Xiaohui, Xu Ke, Xu Xiaolin, Xie Yue, Li Yang
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To investigate the transthyretin (TTR) mutations and clinical characteristics of patients with vitreous amyloidosis.
Ten cases of suspected vitreous amyloidosis were recruited in Beijing Tongren Hospital from January 2011 to December 2018.The patients and their relatives underwent detailed ophthalmologic examination.Genomic DNA was extracted from 4 ml peripheral blood samples of patients and their available family members.The four 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 available family members.The vitreous specimen of 5 patients obtained during vitrectomy was stained with hematoxylin and eosin and Congo red.Written informed consent was obtained from each subject prior to entering the study cohort.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital(No.TRECKY2017-08).
Six reported missense mutations of the TTR gene, p. V30A, p.K35N, p.L55R, p.Y69H, p.G83R, and p. Y114C, were identified in 8 patients.The mutations were 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.Hematoxylin and eosin staining of vitreous specimens in 5 patients showed no structural substance.Congo red staining was positive in one patient.Six of 8 patients showed combined hearing system, autonomic nervous system or peripheral nervous system abnormalities.
The β-strand C is the protein region where common TTR mutations are located.The p. G83R mutation of TTR gene is a mutation hotspot in Chinese patients with vitreous amyloidosis.Mutation screening of the TTR gene can be used to distinguish vitreous amyloidosis from other causes of vitreous opacity.