Familial exudative vitreoretinopathy with <i>TGFBR2</i> mutation without signs of Loeys-Dietz syndrome

Asano, Takeshi; Oku, Kazuma; Kondo, Hiroyuki

doi:10.1080/13816810.2021.1938137

Cited by 11 publications

(5 citation statements)

References 18 publications

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“…Then, we measured DNA concentration with an ultraviolet spectrophotometer NanoDrop ND‐2000C (Thermo Fisher Scientific). Then, we refer to the previous method to perform WES analysis on the samples (Asano et al, 2021 ). The captured library was sequenced on Illumina HiSeq 2500 (Illumina).…”

Section: Methodsmentioning

confidence: 99%

A novel frameshift variant in the TSPAN12 gene causes autosomal dominant FEVR

Dai

Xiao

et al. 2022

Molec Gen & Gen Med

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Background Familial exudative vitreoretinopathy (FEVR) is an inherited blinding eye disease with abnormal retinal vascular development. We aim to broaden the variant spectrum of FEVR and provide a basis for molecular diagnosis and genetic consultation. Methods We recruited five FEVR patients from one large Chinese family. Whole‐exome sequencing (WES) and Sanger sequencing were applied to sequence, analyze, and verify variants on genomic DNA samples. Immunocytochemistry, western blot, qPCR, and luciferase assay were performed to test the influence of the variant on the protein expression and activity of the Norrin/β‐catenin pathway. Results We identified a novel heterozygous frameshift variant c.533dupC (p.D179Rfs*6) in Tetraspanin 12 (TSPAN12) gene that is related to FEVR. This variant caused degradation of the entire TSPAN12 protein, which failed to activate Norrin/β‐catenin signaling, possibly causing FEVR. Conclusion Our study revealed a novel frameshift variant D179Rfs*6 in TSPAN12 that is inherited in an autosomal dominant manner. We found that D179Rfs*6 caused a failure to activate Norrin/β‐catenin signaling. This finding broadens the variant spectrum of TSPAN12 and provides invaluable information for the molecular diagnosis of FEVR.

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Section: Methodsmentioning

confidence: 99%

A novel frameshift variant in the TSPAN12 gene causes autosomal dominant FEVR

Dai

Xiao

et al. 2022

Molec Gen & Gen Med

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“… 12 Other genes have been reported in association with FEVR with and without extraocular manifestations, but with the exception of KIF11, 13 most have been reported in rare cases with variable evidence to support a role in FEVR. 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 …”

Section: Introductionmentioning

confidence: 99%

Multimodal imaging of white preretinal lesions in atypical familial exudative vitreoretinopathy: Case report and literature review

Redden,

Iaboni,

van der Ende

et al. 2024

American Journal of Ophthalmology Case Reports

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“…Due to the significant genetic heterogeneity, FEVR displays all Mendelian forms of inheritance: autosomal dominant (AD), autosomal recessive (AR), or X-linked recessive (XR) [7][8][9] . To date, mutations in 17 genes and 1 locus have been identified to cause FEVR, including Norrin (NDP) [10] , frizzled 4 (FZD4) [11] , low-density lipoprotein receptor related protein 5 (LRP5) [12,13] , low-density lipoprotein receptor-related protein 6 (LRP6) [14] , tetraspanin-12 (TSPAN12) [15,16] , α-catenin (CTNNA1) [17] , β-catenin (CTNNB1) [18][19][20] , p120-catenin (CTNND1) [21] , zinc finger protein 408 (ZNF408) [22] , kinesin family member 11 (KIF11) [23] , atonal homolog 7 (ATOH7) [24] , exudative vitreoretinopathy 3 (EVR3) [25] , integrin-linked kinase (ILK) [26] , jagged canonical Notch ligand 1 (JAG1) [27] , discs large MAGUK scaffold protein 1 (DLG1) [28] , transforming growth factor beta receptor 2 (TGFBR2) [29] , sorting nexin 31 (SNX31) [30] , and ER membrane protein complex subunit 1 (EMC1) [31] . Nevertheless, these mutations can explain only approximately 50% of FEVR cases [32,33] .…”

Section: Introductionmentioning

confidence: 99%

Defective CAPSL function causes impaired retinal angiogenesis through the MYC axis and is associated with familial exudative vitreoretinopathy

Liu,

Li,

Yang

et al. 2024

Preprint

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Familial exudative vitreoretinopathy (FEVR) is a severe genetic disorder characterized by incomplete vascularization of the peripheral retina and associated symptoms that can lead to vision loss. However, the underlying genetic causes of approximately 50% of FEVR cases remain unknown. Here, we report two heterozygous variants, c.88C>T (p.Arg30Ter) and c.247C>T (p.Leu83Phe), in calcyphosine like (CAPSL), from four patients in two unrelated FEVR-affected families. Both variants exhibited compromised CAPSL protein expression. Vascular endothelial cell-specific inactivation ofCapslin postnatal mice resulted in defective sprouting, delayed radial/vertical vascular progression, compromised endothelial proliferation, and impaired cell migration, recapitulating the human FEVR phenotypes.CAPSL-depleted human retinal microvascular endothelial cells (HRECs) exhibited impaired tube formation, decreased cell proliferation, disrupted cell polarity establishment and filopodia/lamellipodia formation, as well as disrupted collective cell migrationin vitro. Transcriptomic and proteomic profiling ofCAPSL-depleted HRECs revealed thatCAPSLabolition inhibited the MYC signaling axis, in which the expression of core MYC targeted genes were profoundly decreased. Furthermore, a combined analysis ofCAPSL-depleted HRECs andc-MYC-depleted human umbilical vein endothelial cells (HUVECs) uncovered similar transcription patterns. Collectively, this study reports a novel FEVR-associated candidate gene,CAPSL, which provides invaluable information for genetic counseling and prenatal diagnosis of FEVR. This study also reveals that compromised CAPSL function causes FEVR through MYC axis, shedding light on the potential involvement of MYC signaling in the pathogenesis of FEVR.

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Familial exudative vitreoretinopathy with TGFBR2 mutation without signs of Loeys-Dietz syndrome

Abstract: Supplementary figure S1. Fluorescein angiographic findings of the parents. a, b, The right and left eyes of the father. c, d, The right and left eyes of the mother. No typical signs of FEVR are observed.

Cited by 11 publications

References 18 publications

A novel frameshift variant in the TSPAN12 gene causes autosomal dominant FEVR

A novel frameshift variant in the TSPAN12 gene causes autosomal dominant FEVR

Multimodal imaging of white preretinal lesions in atypical familial exudative vitreoretinopathy: Case report and literature review

Defective CAPSL function causes impaired retinal angiogenesis through the MYC axis and is associated with familial exudative vitreoretinopathy

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