TTR Gly83Arg Mutation: Beyond Familial Vitreous Amyloidosis

Abstract

BackgroundGly83Arg variation is a type of TTR mutation specific to the Chinese population. Patients of hereditary transthyretin amyloidosis (ATTR) with Gly83Arg variation predominantly present with blurred vision and most of these cases are reported by ophthalmologists. There is currently no systematic assessment of extraocular features of ATTR with Gly83Arg variation.MethodsSix patients and two asymptomatic carriers with molecularly confirmed Gly83Arg variation of ATTR from three unrelated families were identified by sequencing the TTR gene. The clinical, electrophysiological, ultrasonic, and pathological data were collected and analyzed.ResultsThis study included six patients and two carriers with TTR Gly83Arg mutation, all of whom came from the Han nationality of China. The average age of onset for the six patients was 39 years, and the course of disease ranged from 5 to 19 years. All the patients started with blurred vision, which was diagnosed as vitreous opacity (VO). Most of the patients developed sensory-motor polyneuropathies over years or even more than a decade (4–15 years) after VO. However, the heterogeneity of peripheral neuropathies among these patients remained large between families. Autonomic impairment also occurred after VO, with varying degrees of abnormalities seen in the associated autonomic assessments. None of the patients had any symptoms of cardiac impairment, but abnormal results were found in examinations. A combined biopsy of the sural nerve and muscle was also performed. Nerve pathology revealed the moderately reduced myelinated nerve fiber density and muscle pathology showed predominant neurogenic impairment accompanied by possible myogenic impairment.ConclusionsThis is a detailed account of Gly83Arg mutation-related ATTR, focusing on the extraocular presentations of this special variant in Chinese. Clinical features of this variant are early-onset, ocular involvement predominance, neurological, and cardiac involvement along with the disease, and relatively long survival.

Case Report: Hereditary transthyretin (ATTRv) amyloidosis: The p.G103R mutation of the transthyretin gene in a Han Chinese family is associated with vitreous hemorrhage

“…This study demonstrated a p.G103R mutation in the TTR gene of a proband from a Han Chinese family. Coincidentally, this mutation has been previously reported in Chinese families (Chen et al, 2011;Xie et al, 2012;Yuan et al, 2012;Zhang et al, 2013;Liu et al, 2014;Yin et al, 2014;Xie et al, 2017;Li et al, 2021). Like our study, there were no systemic symptoms except for ocular amyloidosis in all family members at its early stage.…”

“…Her daughter (IV-9) was an asymptomatic carrier. This mutation has been reported to be pathogenic and related to ATTRv amyloidosis ( Chen et al, 2011 ; Xie et al, 2012 ; Yuan et al, 2012 ; Zhang et al, 2013 ; Liu et al, 2014 ; Yin et al, 2014 ; Xie et al, 2017 ; Li et al, 2021 ). Based on the clinical manifestation and genetic testing, the patients were diagnosed with ATTRv amyloidosis.…”

“…Most patients with p. G103R have only been reported to have ocular symptoms. Yet extraocular symptoms of the p. G103R mutation were reported in Li et al (2021) ’s study, which involved three families with six patients and two asymptomatic carriers. All the patients started with blurred vision and vitreous amyloidosis, and most of them developed sensory-motor polyneuropathies several years later.…”

Clinical features of retinal amyloid angiopathy with transthyretin Gly83Arg variant

“…A variety of transthyretin (TTR) gene mutation types can cause RAA, and the currently reported mutation types are V30M, Y114C, E54G, R34K, and A36P [4][5][6][7][8] . TTR Gly83Arg is a mutation hotspot in Southwest China, which can lead to hATTR (ATTRG83R amyloidosis) [9] . The ATTRG83R amyloidosis mainly involves the eyes [10] .…”