Mutation P.G83R in the Transthyretin Gene is Associated with Hereditary Vitreous Amyloidosis in Han Chinese Families

Overview

Journal Mol Vis

Specialties Cell Biology
Molecular Biology
Ophthalmology

Date 2013 Aug 1

PMID 23901247

Citations 9

Authors

A-Mei Zhang

Hui Wang

Peng Sun

Qiu-Xiang Hu

Yuqing He

Yong-Gang Yao

Affiliations

Soon will be listed here.

Abstract

Purpose: Hereditary vitreous amyloidosis (HVA) is a genetic ophthalmological disorder. The purpose of this study was to investigate whether a mutation in the transthyretin (TTR) gene is associated with HVA in Han Chinese families.

Methods: We performed clinical evaluation of three Han Chinese families with HVA and sequenced the entire exon of the TTR gene in probands and normal individuals from the families. The identified mutation was further genotyped in 196 unrelated healthy controls. Evolutionary conservation analysis and structural prediction were used to infer the potential pathogenicity of the mutation.

Results: Clinical penetrance of HVA varied in the three families (11/30 in Family A, 8/83 in Family B, and 7/47 in Family C). A comprehensive medical examination of the patients showed no signs of abnormality except ophthalmologic symptoms, in which floccular turbidity and high echo in both vitreous bodies were observed in all probands. Further histochemical examination of the vitrectomy specimen with Congo red staining identified amyloid deposits. A heterozygous mutation c.307G>C (p.G83R) in exon 3 of the TTR gene was identified in all patients, but not in some unaffected family members. Screening of 196 unrelated normal controls revealed no presence of this mutation. This mutation changed the highly conserved glycine to arginine in the 83(rd) position and altered the tertiary structure of the TTR protein.

Conclusions: Mutation p.G83R in the TTR protein is associated with HVA in Chinese families. The seemingly specific distribution of this mutation in Han Chinese may be used for clinical diagnosis.

Citing Articles

Hereditary vitreoretinal amyloidosis with transthyretin Gly83Arg variant, a long-term study.

Chen X, Xin C, Su G, Xie B, Li H, Ren H Eye (Lond). 2024; 39(2):345-353.

PMID: 39478196 PMC: 11750974. DOI: 10.1038/s41433-024-03445-y.

The Gly103Arg variant in hereditary transthyretin amyloidosis.

Xiong Y, Qu G, Lu X, Chang X, Zhang M, Liang J Front Neurol. 2024; 15:1471131.

PMID: 39314866 PMC: 11416968. DOI: 10.3389/fneur.2024.1471131.

Rare manifestation of familial vitreous amyloidosis caused by Gly103Arg transthyretin.

Feng Y, Shi Y, He Y, Ma Z, Zhu Y, Weng W Int J Ophthalmol. 2023; 16(7):1093-1099.

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

Shen J, Yu H, Lin J, Zhang L, Pan X, Chen Z Front Genet. 2022; 13:972501.

PMID: 36186469 PMC: 9520364. DOI: 10.3389/fgene.2022.972501.

Clinical phenotypes and genetic features of hereditary transthyretin amyloidosis patients in China.

He X, Tian Z, Guan H, Zhang S Orphanet J Rare Dis. 2022; 17(1):337.

PMID: 36056432 PMC: 9438301. DOI: 10.1186/s13023-022-02481-9.

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