title: Mutation p.G83R in the transthyretin gene is associated with hereditary vitreous amyloidosis in Han Chinese families.
abstract: OBJECTIVE
  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.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
authors.forename: A-Mei
authors.initials: AM
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.forename: Qiu-Xiang
authors.initials: QX
authors.lastname: Hu
authors.forename: Yuqing
authors.initials: Y
authors.lastname: He
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Yao
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D028226:Amyloidosis, Familial / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002681:China; D004272:DNA, Mitochondrial / Q000235:genetics; D005006:Ethnicity / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011228:Prealbumin / Q000737:chemistry / Q000235:genetics*; D040681:Structural Homology, Protein; D014822:Vitreous Body / Q000473:pathology*
chemical_list: D004272:DNA, Mitochondrial; D011228:Prealbumin
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