title: Transthyretin Ala36Pro mutation in a Chinese pedigree of familial transthyretin amyloidosis with elevated vitreous and serum vascular endothelial growth factor.
abstract: The familial transthyretin (TTR) amyloidosis (FTA) demonstrates variable penetrance of clinical features associated with mutations in the plasma thyroid hormone-binding protein TTR gene. The purpose of this study was to assess the ocular features, to analyze vitreous and serum vascular endothelial growth factor (VEGF) levels, and to identify the genetic defect in a Chinese family with TTR FTA. The pedigree of interest was a three-generation family with eleven members. The primary ocular signs were vitreous opacities, beginning from the third or fourth decade, accompanied by retinal vasculitis, hemorrhages, and widespread pinpoint deposits in the peripheral retina. Two patients underwent vitrectomy with marked improvement of visual acuity postoperatively. Vitreous and serum samples for VEGF were analyzed with an enzyme-linked immunosorbent assay (ELISA). Forty-eight healthy adult volunteers were enrolled as a control group for the analysis of serum VEGF. Eight subjects who underwent vitrectomy for a macular epiretinal membrane or macular hole were enrolled as control for the analysis of vitreous VEGF. Both serum and vitreous VEGF levels of patients were raised compared to that of controls. Venous blood was collected from family members and the genomic DNA was extracted. All exons and exon-intron boundaries of the TTR gene were sequenced. A previously-described pathogenic transversion in exon 2 (c.G106C, p.Ala36Pro) was identified. Within this family eight individuals were confirmed as affected. In conclusion, a Chinese family with TTR Ala36Pro associated FTA is characterized by early ocular involvement. Widespread pinpoint lesions indicate RPE lesions caused by TTR deposition. FTA is associated with increased VEGF levels, both in serum and vitreous.
authors: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan Road, Dongcheng District, Beijing 100710, China.
authors: Xuan
authors: X
authors: Zou
authors: Fangtian
authors: F
authors: Dong
authors: Shuying
authors: S
authors: Zhang
authors: Rong
authors: R
authors: Tian
authors: Ruifang
authors: R
authors: Sui
mesh_terms: D000328:Adult; D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics*; D004252:DNA Mutational Analysis; D004585:Electrooculography; D004596:Electroretinography; D004797:Enzyme-Linked Immunosorbent Assay; D005128:Eye Diseases / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011228:Prealbumin / Q000235:genetics*; D012166:Retinal Hemorrhage / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D031300:Retinal Vasculitis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D041623:Tomography, Optical Coherence; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D014792:Visual Acuity / Q000502:physiology; D014821:Vitrectomy; D014822:Vitreous Body / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D011228:Prealbumin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A