AUTHOR=Li Zhenxian , Du Kang , Chu Xujun , Lv He , Zhang Wei , Wang Zhaoxia , Yuan Yun , Meng Lingchao 

TITLE=TTR Gly83Arg Mutation: Beyond Familial Vitreous Amyloidosis

JOURNAL=Frontiers in Neurology

VOLUME=Volume 12 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.821003

DOI=10.3389/fneur.2021.821003

ISSN=1664-2295

ABSTRACT=Background: Gly83Arg 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 were reported by ophthalmologists. There is currently no systematic assessment of extraocular features of ATTR with Gly83Arg variation.
Methods：Six 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.
Results: This study included six patients and two carriers who were positive for missense mutation in TTR (c.307G＞C, p.Gly83Arg), 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). All the patients developed peripheral nerve damage over a period of several years or even more than a decade (4-17 years). However, the heterogeneity of peripheral nerve damage 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 the examination. Combined biopsy of sural nerve and muscle was also performed. Nerve pathology revealed the moderately reduced myelinated fiber density and muscle pathology showed predominant neurogenic impairment accompanied by myogenic impairment.
Conclusions: This is a detailed account of Gly83Arg mutation related ATTR that focused on the extraocular presentations of this special variant in Chinese. Clinical features of this variant were early onset, ocular involvement predominance, neurological and cardiac involvement along with the disease, and relatively long survival. 
Keywords: Transthyretin amyloidosis, Gly83Arg, China, Ocular symptoms, Extraocular symptoms.