TTR Gly83Arg Mutation: Beyond Familial Vitreous Amyloidosis.

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

doi:10.3389/fneur.2021.821003

Zhenxian Li, Wei Zhang + Show 6 more

Open Access

https://doi.org/10.3389/fneur.2021.821003

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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.

Highlights

Hereditary amyloidosis is a group of genetic diseases characterized by tissue deposition of insoluble proteins and fibril aggregates, causing disorders involving different organs
Six patients and two asymptomatic carriers from three unrelated families who were diagnosed with Gly83Arg variation of ATTR at the Department of Neurology, Peking University First Hospital, between September 2019 and April 2021 were included in this study
All the six patients were of Chinese Han nationality, including three females (I-1,2,3) and three males (II-4, III-5,6), with the pathogenic variation of TTR c.307G>C, p.Gly103Arg (Gly83Arg) (Figure 1)

Summary

Introduction

Hereditary amyloidosis is a group of genetic diseases characterized by tissue deposition of insoluble proteins and fibril aggregates, causing disorders involving different organs. Hereditary transthyretin amyloidosis (ATTR), caused by TTR gene mutations, is characterized by a length-dependent polyneuropathy and autonomic dysfunction, with multisystem involvement, namely, the heart, eyes, and kidney [1]. Gly83Arg, a unique TTR gene mutation in the Chinese population, is characterized by ocular involvement, which has been discovered and reported by ophthalmologists in recent years. It is considered as a mutation, causing familial vitreous amyloidosis [3,4,5,6,7,8,9]. 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

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Conclusion