Chinese familial transthyretin amyloidosis with vitreous involvement is associated with the transthyretin mutation Gly83Arg: a case report and literature review

Yin, Jie; Xia, Xinyi; Shi, Yu; Lu, Yan; Zhao, Changlin; Huang, Zhenping; Tian, Ning

doi:10.3109/13506129.2014.892871

Cited by 10 publications

(14 citation statements)

References 7 publications

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“…In our patients, Val30Met was the most common genotype which was consistent with foreign reports. [ 5 ] Val30Ala, Ala97Ser, and Gly83Arg are recognized as the most common amyloidogenic forms in Chinese patients,[ 18 ] but in our patients only Val30Ala appeared in one family. The reasons explaining the discrepancy may be that patients with TTR Gly83Arg mutant, indicating solitary ocular vitreous amyloidosis, without the evidence of systemic involvement, often came from the Department of Ophthalmology,[ 18 ] while Ala97Ser may be common in Chinese patients.…”

Section: Discussionmentioning

confidence: 62%

“…[ 5 ] Val30Ala, Ala97Ser, and Gly83Arg are recognized as the most common amyloidogenic forms in Chinese patients,[ 18 ] but in our patients only Val30Ala appeared in one family. The reasons explaining the discrepancy may be that patients with TTR Gly83Arg mutant, indicating solitary ocular vitreous amyloidosis, without the evidence of systemic involvement, often came from the Department of Ophthalmology,[ 18 ] while Ala97Ser may be common in Chinese patients. [ 19 ] Some mutations indicating special clinical phenotypes such as familial carpal tunnel syndrome (Tyr114His) and predominant cardiomyopathy (Ala45Ser) proved the genotype-phenotype correlation,[ 20 21 ] while sometimes the same genotypes show different phenotypes just like the family of patient 5.…”

Section: Discussionmentioning

confidence: 77%

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Hereditary Transthyretin Amyloidosis in Eight Chinese Families

Meng

Lyu

Zhang

et al. 2015

Chinese Medical Journal

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Background:Mutations of transthyretin (TTR) cause the most common type of autosomal-dominant hereditary systemic amyloidosis, which occurs worldwide. To date, more and more mutations in the TTR gene have been reported. Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family. The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis.Methods:Clinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014. Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients, for light and electron microscopy examination. The TTR genes from the nine patients were analyzed.Results:The onset age varied from 23 to 68 years. The main manifestations were paresthesia, proximal and/or distal weakness, autonomic dysfunction, cardiomyopathy, vitreous opacity, hearing loss, and glossohypertrophia. Nerve biopsy demonstrated severe loss of myelinated fibers in seven cases and amyloid deposits in three. One patient had skin amyloid deposits which were revealed from electron microscopic examination. Genetic analysis showed six kinds of mutations of TTR gene, including Val30Met, Phe33Leu, Ala36Pro, Val30Ala, Phe33Val, and Glu42Gly in exon 2.Conclusions:Since the pathological examinations of sural nerve were negative for amyloid deposition in most patients, the screening for TTR mutations should be performed in all the adult patients, who are clinically suspected with hereditary TTR amyloidosis.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 77%

Hereditary Transthyretin Amyloidosis in Eight Chinese Families

Meng

Lyu

Zhang

et al. 2015

Chinese Medical Journal

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“…Two well-documented cases are an altered vitreous proteome in proliferative diabetic retinopathy and the vitreous deposition of amyloid in systemic amyloidosis. [ 6 – 12 ] Therefore, gene expression analysis of local eye tissues or the few resident hyalocyte cells could fail to account for many vitreous proteins in normal and disease states. Proteomic analysis circumvents this pitfall by identifying every expressed protein within a tissue, regardless of its site of synthesis.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Insight into the Molecular Function of the Vitreous

2015

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The human vitreous contains primarily water, but also contains proteins which have yet to be fully characterized. To gain insight into the four vitreous substructures and their potential functions, we isolated and analyzed the vitreous protein profiles of three non-diseased human eyes. The four analyzed substructures were the anterior hyaloid, the vitreous cortex, the vitreous core, and the vitreous base. Proteins were separated by multidimensional liquid chromatography and identified by tandem mass spectrometry. Bioinformatics tools then extracted the expression profiles, signaling pathways, and interactomes unique to each tissue. From each substructure, a mean of 2,062 unique proteins were identified, with many being differentially expressed in a specific substructure: 278 proteins were unique to the anterior hyaloid, 322 to the vitreous cortex, 128 to the vitreous base, and 136 to the vitreous core. When the identified proteins were organized according to relevant functional pathways and networks, key patterns appeared. The blood coagulation pathway and extracellular matrix turnover networks were highly represented. Oxidative stress regulation and energy metabolism proteins were distributed throughout the vitreous. Immune functions were represented by high levels of immunoglobulin, the complement pathway, damage-associated molecular patterns (DAMPs), and evolutionarily conserved antimicrobial proteins. The majority of vitreous proteins detected were intracellular proteins, some of which originate from the retina, including rhodopsin (RHO), phosphodiesterase 6 (PDE6), and glial fibrillary acidic protein (GFAP). This comprehensive analysis uncovers a picture of the vitreous as a biologically active tissue, where proteins localize to distinct substructures to protect the intraocular tissues from infection, oxidative stress, and energy disequilibrium. It also reveals the retina as a potential source of inflammatory mediators. The vitreous proteome catalogues the dynamic interactions between the vitreous and surrounding tissues. It therefore could be an indirect and effective method for surveying vitreoretinal disease for specific biomarkers.

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“…However, it is recorded in the Mutations in Hereditary Amyloidosis database as being amyloidogenic [5] and its similarity to the p.Thr80Ala variant suggests that its clinical implications might be predicted (Table 2). Interestingly, some p.Ile88Leu, which is seen predominantly in the Italian population [8,24] and has primarily cardiac manifestations [24]; p.Val50Ala, p.Ala117Ser and p.Gly103Arg, the most common amyloidogenic variants in the Chinese population [25]; and p.Ser70Arg, the most common variant in Mexico [26]. The absence of these variants from our database does not imply that they are absent in the Saudi population.…”

Section: Discussionmentioning

confidence: 97%

Data Mining for the Identification of Known and Candidate Transthyretin Amyloidosis Variants in the Saudi Population

Abouelhoda

Mohty

Alayary

et al. 2021

Preprint

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BackgroundFamilial transthyretin (TTR) amyloidosis (ATTR) is an autosomal dominant disease with significant phenotypic heterogeneity. Its prevalence in Saudi Arabia has not previously been investigated. An existing exome variant database of Saudi individuals, sequenced to globally investigate rare diseases in the population, was mined for TTR variants and filtered for missense mutations resulting in single amino acid changes. A total of 13,906 Saudi exomes from unrelated individuals were analyzed blindly. ResultsThree TTR variants known to be associated with ATTR amyloidosis were identified. Additionally, three novel TTR mutations were identified. Structural analysis of the three novel variants suggests that at least two could be amyloidogenic. The most common variant associated with amyloidosis was p.Val142Ile (allele frequency 0.001). Further investigation of these variants and their translation to clinical practice may help to diagnose, monitor and manage patients with ATTR amyloidosis.ConclusionMultiple TTR variants potentially associated with systemic ATTR amyloidosis were identified in the Saudi population. Early diagnosis and intervention, facilitated by familial genetic testing of patients with ATTR amyloidosis, may benefit in the management of this disease. Early diagnosis could be enhanced through inclusion of ATTR variants in existing population-based screening programs.

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Chinese familial transthyretin amyloidosis with vitreous involvement is associated with the transthyretin mutation Gly83Arg: a case report and literature review

Cited by 10 publications

References 7 publications

Hereditary Transthyretin Amyloidosis in Eight Chinese Families

Hereditary Transthyretin Amyloidosis in Eight Chinese Families

Proteomic Insight into the Molecular Function of the Vitreous

Data Mining for the Identification of Known and Candidate Transthyretin Amyloidosis Variants in the Saudi Population

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