Clinical Science
Genetic testing and clinical phenotypic analysis of familial vitreous amyloidosis in two Han Chinese families
Zheng Wei, Li Haibo, Zhang Xueyong, Zhou Xuezhi, Chen Yuanyuan, Mao Junfeng
Published 2021-08-10
Cite as Chin J Exp Ophthalmol, 2021, 39(8): 714-718. DOI: 10.3760/cma.j.cn115989-20190721-00318
Abstract
ObjectiveTo investigate the clinical characteristics of two Han families with familial vitreous amyloidosis (FVA) and the gene mutation.
MethodsA pedigree investigation was performed.Two Han Chinese families with FVA treated in Xiangya Hospital of Central South University from January 2015 to December 2018 were collected.General examination and ophthalmic examination were performed among 112 members of the two families.Peripheral blood samples were collected from 32 family members (15 patients in MZ001 pedigree, 7 patients in MZ002 pedigree, and 5 persons with normal clinical phenotype from each pedigree) for DNA extraction, polymerase chain reaction (PCR) amplification, transthyretin (TTR) gene screening and sequencing.Vitreous biopsy following three-channel 23-gauge pars plana vitrectomy was performed on the two probands in the two families.Vitreous specimens were sent for pathological examination.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Xiangya Hospital of Central South University (No.201412463), and written informed consent was obtained from all subjects before any medical examination.
ResultsIn MZ001, there were 15 cases of the 63 members presented bilateral vitreous opacity at an average age of (43.6±5.8) years.No lesion was found in nervous system, cardiovascular system, kidney or liver in general inspection.The vitreous of the proband (Ⅲ13) was so sticky that could not be totally removed during vitrectomy.The vitreous specimen showed positive Congo red staining.Ⅲ13 had elevated intraocular pressure after vitrectomy and was diagnosed as open-angle glaucoma.Gene sequencing revealed Gly83Arg mutation in the exon 3 of TTR gene.In MZ002, 7 cases of 49 members had bilateral vitreous opacity at an average age of (50.4±5.5) years, among which, 3 cases appeared symptoms of limb numbness and decreased muscle strength.The vitreous body of the proband (Ⅱ11) in MZ002 pedigree was looser and easier to remove during vitrectomy than that of Ⅲ13 in MZ001 pedigree.Vitreous specimen of Ⅱ11 was positive with Congo red staining.Gene sequencing revealed an Ala36Pro variant in the exon 3 of TTR gene.
ConclusionsGly83Arg or Ala36Pro mutation of TTR gene can cause FVA.Different mutations can lead to different clinical phenotypes such as age of onset, clinical symptoms and complications of other systems.
Key words:
Vitreous amyloidosis; Clinical phenotype; Transthyretin; Genetic mutation; Han nationality; Pedigree study
Contributor Information
Zheng Wei
Department of Ophthalmology, Xiangya Hospital of Central South University, Changsha 410008, China
Li Haibo
Department of Ophthalmology, Xiangya Hospital of Central South University, Changsha 410008, China
Zhang Xueyong
Department of Ophthalmology, Xiangya Hospital of Central South University, Changsha 410008, China
Zhou Xuezhi
Department of Ophthalmology, Xiangya Hospital of Central South University, Changsha 410008, China
Chen Yuanyuan
Department of Ophthalmology, Xiangya Hospital of Central South University, Changsha 410008, China
Mao Junfeng
Department of Ophthalmology, Xiangya Hospital of Central South University, Changsha 410008, China
