Zhang A-Mei, Wang Hui, Sun Peng, Hu Qiu-Xiang, He Yuqing, Yao Yong-Gang
Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
Mol Vis. 2013 Jul 25;19:1631-8. Print 2013.
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.
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.
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.
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.
遗传性玻璃体淀粉样变性（HVA）是一种遗传性眼科疾病。本研究旨在调查转甲状腺素蛋白（TTR）基因的突变是否与汉族家庭中的HVA相关。
我们对三个患有HVA的汉族家庭进行了临床评估，并对先证者和家庭中的正常个体的TTR基因的整个外显子进行了测序。在196名无亲缘关系的健康对照中对鉴定出的突变进行了进一步的基因分型。使用进化保守性分析和结构预测来推断该突变的潜在致病性。
HVA的临床外显率在三个家庭中有所不同（A家族为11/30，B家族为8/83，C家族为7/47）。对患者进行的全面医学检查显示，除眼科症状外无异常迹象，所有先证者均观察到玻璃体絮状混浊和高回声。用刚果红染色对玻璃体切除标本进行进一步的组织化学检查，发现了淀粉样沉积物。在所有患者中均鉴定出TTR基因第3外显子的杂合突变c.307G>C（p.G83R），但在一些未受影响的家庭成员中未发现。对196名无亲缘关系的正常对照进行筛查，未发现该突变。该突变将第83位高度保守的甘氨酸变为精氨酸，并改变了TTR蛋白的三级结构。
TTR蛋白中的p.G83R突变与中国家庭中的HVA相关。这种突变在汉族人中看似特定的分布可用于临床诊断。
