Whole-Exome Sequencing in a Cohort of High Myopia Patients in Northwest China

Liu, Yang; Zhang, Jinjin; Piao, Shun-Yu; Shen, Ren‐Juan; Ma, Ya; Xue, Zhongqi; Zhang, Wen; Liu, Juan; Zhuang, Wenjuan

doi:10.3389/fcell.2021.645501

Cited by 9 publications

(8 citation statements)

References 55 publications

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“…The identification of pathogenic mutations in these genes promises to significantly enrich our understanding of the pathogenesis of HM. 19 …”

Section: Discussionmentioning

confidence: 99%

“… 18 Another study recruited 27 eoHM families from the Ningxia Hui Autonomous Region, uncovering mutations in four genes ( CSMD1 , PARP8 , ADAMTSL1 and FNDC3B ). 19 Wang et al investigated 14 eoHM genes in a sizeable cohort and revealed ARR3 as the most common cause of Mendelian eoHM. 20 However, current genetic research on myopia across various provinces in China is insufficient, particularly in Shaanxi province, which is known for its high incidence of the condition (54.9% prevalence of myopia).…”

Section: Introductionmentioning

confidence: 99%

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Trio-based whole-exome sequencing reveals mutations in early-onset high myopia

Ye,

Guo,

Cai

et al. 2024

BMJ Open Ophth

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PurposeMyopia, especially high myopia (HM), represents a widespread visual impairment with a globally escalating prevalence. This study aimed to elucidate the genetic foundations associated with early-onset HM (eoHM) while delineating the genetic landscape specific to Shaanxi province, China.MethodsA comprehensive analysis of whole-exome sequencing was conducted involving 26 familial trios displaying eoHM. An exacting filtration protocol identified potential candidate mutations within acknowledged myopia-related genes and susceptibility loci. Subsequently, computational methodologies were employed for functional annotations and pathogenicity assessments.ResultsOur investigation identified 7 genes and 10 variants associated with HM across 7 families, including a novel mutation in theARR3gene (c.139C>T, p.Arg47*) and two mutations in theP3H2gene (c.1865T>C, p.Phe622Ser and c.212T>C, p.Leu71Pro). Pathogenic mutations were found in syndromic myopia genes, notably encompassingVPS13B,TRPM1, RPGR,NYXandRP2. Additionally, a thorough comparison of previously reported causative genes of syndromic myopia and myopia risk genes with the negative sequencing results pinpointed various types of mutations within risk genes.ConclusionsThis investigation into eoHM within Shaanxi province adds to the current understanding of myopic genetic factors. Our results warrant further functional validation and ocular examinations, yet they provide foundational insights for future genetic research and therapeutic innovations in HM.

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“…The identification of pathogenic mutations in these genes promises to significantly enrich our understanding of the pathogenesis of HM. 19 …”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Trio-based whole-exome sequencing reveals mutations in early-onset high myopia

Ye,

Guo,

Cai

et al. 2024

BMJ Open Ophth

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“…Previous evidence supported that high myopia facilitates the formation of cataracts [ 12 ]. Myopia is also coregulated by genetic and environmental factors [ 13 ]. Thus, genetic factors are indicated to contribute to the pathogenesis of high myopia-induced cataracts (HMC).…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in TRIB2 and CAPRIN2 Genes Contribute to the Susceptibility to High Myopia-Induced Cataract in Han Chinese Population

Zhang

Wang

et al. 2023

Med Sci Monit

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Background Myopia has been shown to be associated with many pathological complications including cataracts, and previous evidence supported that high myopia facilitates the formation of cataracts. However, no studies have identified a link between the genetic susceptibility of high myopia-induced cataracts (HMC) and the underlying genetic mechanisms. Our study aimed to determine how the TRIB2 and CAPRIN2 genes correlate to the risk of HMC. Material/Methods In total, we successfully recruited 3162 participants, including 1026 participants with high myopia and cataracts and 2136 controls with high myopia only. For genotyping, 22 tag single nucleotide polymorphisms (SNPs) in TRIB2 and CAPRIN2 genes were chosen. Single marker association analysis and functional effects of significant SNPs were carried out. Results Strong correlation signals were captured for SNP rs890069 (χ 2 =22.13, P =2.55×10 −6 ) in TRIB2 and SNP rs17739338 (χ 2 =16.07, P =6.10×10 −5 ) in CAPRIN2 . In patients with high myopia, the C allele at SNP rs890069 was strongly linked to cataract risk (OR [95% CI]=1.36 [1.20–1.55]). In patients with high myopia, the T allele at SNP rs17739338 was significantly related to a lower risk of cataract (OR [95% CI]=0.54 [0.40–0.74]). In different types of human tissues, SNPs rs890069 and rs17739338 were found to be significantly correlated to the levels of TRIB2 and CAPRIN2 gene expression. Conclusions Our study indicated that both TRIB2 and CAPRIN2 genes conferred the susceptibility to cataract in patients with high myopia and Chinese Han ancestry. Future research remains necessary for fully understanding the pathogenic mechanisms and genetic characteristics of cataract.

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“… 58 For instance, a WES study involving 27 families has uncovered 201 candidate variants associated with HM. 59 Additionally, our previous study has shown that population-based WES can discover functional risk alleles and provide important clues to elucidate the cause of HM. 60 Therefore, large-scale genetic screening for school-aged children with HM could provide further insight into the intersecting contributions of biology and the environment.…”

Section: Introductionmentioning

confidence: 99%

Whole-Exome Sequencing Among School-Aged Children With High Myopia

Yu,

Yuan,

Chen

et al. 2023

JAMA Netw Open

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ImportanceHigh myopia (HM) is one of the leading causes of visual impairment worldwide. Genetic factors are known to play an important role in the development of HM.ObjectiveTo identify risk variants in a large HM cohort and to examine the implications of genetic testing of schoolchildren with HM.Design, Setting, and ParticipantsThis cohort study retrospectively reviewed whole-exome sequencing (WES) results in 6215 schoolchildren with HM who underwent genetic testing between September 2019 and July 2020 in Wenzhou City, China. HM is defined as a spherical equivalent refraction (SER) of −6.00 diopters (D) or less. The study setting was a genetic testing laboratory and a multicenter school census. Data were analyzed from July 2021 to June 2022.Main Outcomes and MeasuresThe frequency and distribution of positive germline variants, the percentage of individuals with HM in both eyes, and subsequent variant yield for common high myopia (CHM; −8.00 D ≤ SER ≤ −6.00 D), ultra myopia (UM; −10.00 D ≤ SER &lt; −8.00 D), and extreme myopia (EM; SER &lt; −10.00 D).ResultsOf the 6215 schoolchildren with HM, 3278 (52.74%) were male. Their mean (SD) age was 14.87 (2.02) years, including 355 students in primary school, 1970 in junior high school, and 3890 in senior high school. The mean (SD) SER was −7.51 (−1.36) D for the right eye and −7.46 (−1.34) D for the left eye. Among schoolchildren with HM, genetic testing yielded 271 potential pathogenic variants in 75 HM candidate genes in 964 diagnoses (15.52%). A total of 36 known variants were found in 490 HM participants (7.88%) and 235 protein-truncating variants (PTVs) in 506 participants (8.14%). Involved variant yield was significantly positively associated with SER (Cochran-Armitage test for trend Z = 2.5492; P = .01), which ranged from 7.66% in the CHM group, 8.70% in the UM group, to 11.90% in the EM group. We also found that primary school students with EM had the highest variant yield of PTVs (8 of 35 students [22.86%]), which was 1.77 and 4.78 times that of the UM and CHM, respectively.Conclusions and RelevanceIn this cohort study of WES for HM, several potential pathogenic variants were identified in a substantial number of schoolchildren with HM. The high variation frequency in younger students with EM can provide clues for genetic screening and clinical examinations of HM to promote long-term follow-up assessment.

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Whole-Exome Sequencing in a Cohort of High Myopia Patients in Northwest China

Cited by 9 publications

References 55 publications

Trio-based whole-exome sequencing reveals mutations in early-onset high myopia

Trio-based whole-exome sequencing reveals mutations in early-onset high myopia

Polymorphisms in TRIB2 and CAPRIN2 Genes Contribute to the Susceptibility to High Myopia-Induced Cataract in Han Chinese Population

Whole-Exome Sequencing Among School-Aged Children With High Myopia

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