Prevalence of transforming growth factor β–induced gene corneal dystrophies in Chinese refractive surgery candidates

Song, Yanzheng; Sun, Manyi; Wang, Ke; Zhou, Xingtao; Zhao, Jing; Wang, Qinmei; Chen, Shihao; Deng, Yingping; Qiu, Lemei; Chen, Yueguo; Aldave, Anthony J.; Zhang, Fengju

doi:10.1016/j.jcrs.2017.07.038

Cited by 6 publications

(5 citation statements)

References 14 publications

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“…The reported prevalence of TGFBI corneal dystrophies in Asia is one in 870 in Korea [13] and one in 416 in China [14]. Asia has a high myopia rate, and a study conducted by Holden et al predicted that by 2050, the Asian-Pacific population will have the highest myopia prevalence rate among all populations at 66.4% compared to the global prevalence of 49.8% [12].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of TGFBI corneal dystrophy and molecular diagnostic testing

Chao-Shern

DeDionisio²,

Jang³

et al. 2019

Eye

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To date, 70 different TGFBI mutations that cause epithelial-stromal corneal dystrophies have been described. At present one commercially available test examines for the five most common of these mutations: R124H, R124C, R124L, R555W, and R555Q. To expand the capability of identifying the causative mutation in the remaining cases, 57 mutations would need to be added. The aim of this study was to obtain a better understanding of the worldwide distribution and population differences of TGFBI mutations and to assess which mutations could be included or excluded from any potential assay. A total of 184 published papers in Human Gene Mutation Database (HGMD) and PubMed from 34 countries worldwide reporting over 1600 corneal dystrophy cases were reviewed. Global data from 600,000 samples using the commercially available test were analyzed. Case studies by University College of London (UCL), Moorfield’s Corneal Dystrophy Study data and 19 samples from patients with clinical abnormality or uncertainty for which the current test detected no mutation were used to predict an achievable detection rate. Data from the literature search showed no difference in the spectrum and frequency of each mutation in different populations or geographical locations. According to our analysis, an increase to the worldwide detection rate in all populations from 75 to 90% could be achieved by the addition of six mutations—H626R, A546D, H572R, G623D, R124S, and M502V—to the currently available test and that may be beneficial for LASIK pre-screening worldwide.

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Section: Discussionmentioning

confidence: 99%

Evaluation of TGFBI corneal dystrophy and molecular diagnostic testing

Chao-Shern

DeDionisio²,

Jang³

et al. 2019

Eye

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“…• GCD2 in the South Korean population: 1 in 870 (Lee et al, 2010) • Five most common TGFBI-linked corneal dystrophies in the Chinese population: 1 in 476 (Song et al, 2017) • Overall corneal dystrophies in the US population according to insurance claims data: 1 in 1115 (Musch et al, 2011)…”

Section: Epidemiologymentioning

confidence: 99%

Biochemical mechanisms of aggregation in TGFBI-linked corneal dystrophies

Nielsen

Poulsen

Lukassen

et al. 2020

Progress in Retinal and Eye Research

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Transforming growth factor-β-induced protein (TGFBIp), an extracellular matrix protein, is the second most abundant protein in the corneal stroma. In this review, we summarize the current knowledge concerning the expression, molecular structure, binding partners, and functions of human TGFBIp. To date, 74 mutations in the transforming growth factor-β-induced gene (TGFBI) are associated with amyloid and amorphous protein deposition in TGFBI-linked corneal dystrophies. We discuss the current understanding of the biochemical mechanisms of TGFBI-linked corneal dystrophies and propose that mutations leading to granular corneal dystrophy (GCD) decrease the solubility of TGFBIp and affect the interactions between TGFBIp and components of the corneal stroma, whereas mutations associated with lattice corneal dystrophy (LCD) lead to a destabilization of the protein that disrupts proteolytic turnover, especially by the serine protease HtrA1. Future research should focus on TGFBIp function in the cornea, confirmation of the biochemical mechanisms in vivo, and the development of disease models. Future therapies for TGFBI-linked corneal dystrophies might include topical agents that regulate protein aggregation or gene therapy that targets the mutant allele by CRISPR/Cas9 technology.

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“…Slit-lamp examinations of four cases with corneal opacity in both eyes and one case without corneal opacity were detected with heterozygous p.R124H mutation of TGFBI. The prevalence rate was 0.24% (5/2068 = 24.2/10,000; Song Y. et al, 2017). Analysis of commercial test data used for pre-refractive surgery screening from 600,000 samples from around the world, most of which are from Korea and Japan, demonstrated that the detection rate of TGFBI CDs in Korea is approximately 15/10,000, which is similar to the previously reported detection rate in the Korean population, which is about 11.5/10,000, and higher than the detection rate in the Japanese population 3/10,000 (Lee et al, 2010;Chao-Shern et al, 2019).…”

Section: Discussionmentioning

confidence: 96%

Evaluation of the Genetic Variation Spectrum Related to Corneal Dystrophy in a Large Cohort

et al. 2021

Front. Cell Dev. Biol.

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AimsTo characterize the genetic landscape and mutation spectrum of patients with corneal dystrophies (CDs) in a large Han ethnic Chinese Cohort with inherited eye diseases (IEDs).MethodsRetrospective study. A large IED cohort was recruited in this study, including 69 clinically diagnosed CD patients, as well as other types of eye diseases patients and healthy family members as controls. The 792 genes on the Target_Eye_792_V2 chip were used to screen all common IEDs in our studies, including 22 CD-related genes.ResultsWe identified 2334 distinct high-quality variants on 22 CD-related genes in a large IEDs cohort. A total of 21 distinct pathogenic or likely pathogenic mutations were identified, and the remaining 2313 variants in our IED cohort had no evidence of CD-related pathogenicity. Overall, 81.16% (n = 56/69) of CD patients received definite molecular diagnoses, and transforming growth factor-beta-induced protein (TGFBI), CHTS6, and SLC4A11 genes covered 91.07, 7.14, and 1.79% of the diagnosed cases, respectively. Twelve distinct disease-associated mutations in the TGFBI gene were identified, 11 of which were previously reported and one is novel. Four of these TGFBI mutations (p.D123H, p.M502V, p.P501T, and p.P501A) were redefined as likely benign in our Han ethnic Chinese IED cohort after performing clinical variant interpretation. These four TGFBI mutations were detected in asymptomatic individuals but not in CD patients, especially the previously reported disease-causing mutation p.P501T. Among 56 CD patients with positive detected mutations, the recurrent TGFBI mutations were p.R124H, p.R555W, p.R124C, p.R555Q, and p.R124L, and the proportions were 32.14, 19.64, 14.29, 10.71, and 3.57%, respectively. Twelve distinct pathogenic or likely pathogenic mutations of CHTS6 were detected in 28 individuals. The recurrent mutations were p.Y358H, p.R140X, and p.R205W, and the proportions were 25.00, 21.43, and 14.29%, respectively. All individuals associated with TGFBI were missense mutations; 74.19% associated with CHTS6 mutations were missense mutations, and 25.81% were non-sense mutations. Hot regions were located in exons 4 and 12 of TGFBI individuals and located in exon 3 of CHTS6 individuals. No de novo mutations were identified.ConclusionFor the first time, our large cohort study systematically described the variation spectrum of 22 CD-related genes and evaluated the frequency and pathogenicity of all 2334 distinct high-quality variants in our IED cohort. Our research will provide East Asia and other populations with baseline data from a Han ethnic population-specific level.

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Prevalence of transforming growth factor β–induced gene corneal dystrophies in Chinese refractive surgery candidates

Cited by 6 publications

References 14 publications

Evaluation of TGFBI corneal dystrophy and molecular diagnostic testing

Evaluation of TGFBI corneal dystrophy and molecular diagnostic testing

Biochemical mechanisms of aggregation in TGFBI-linked corneal dystrophies

Evaluation of the Genetic Variation Spectrum Related to Corneal Dystrophy in a Large Cohort

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