Does the Association Between<i>TMEM98</i>and Nanophthalmos Require Further Confirmation?

Sun, Wenmin; Zhang, Qingjiong

doi:10.1001/jamaophthalmol.2014.4915

Cited by 9 publications

(6 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Caution in assigning a role for TMEM98 in nanophthalmos has been raised by findings in another study in which different heterozygous missense mutations in TMEM98 were found in patients with high myopia and cone-rod dystrophy. 14 Patients with heterozygous or homozygous mutations in the BEST1 gene can have a range of defects. 15 BEST1 encodes the bestrophin-1 protein, a transmembrane protein located in the basolateral membrane of the RPE.…”

mentioning

confidence: 99%

Missense Mutations in the Human Nanophthalmos GeneTMEM98Cause Retinal Defects in the Mouse

Cross

McKie

Keighren

et al. 2019

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Citation: Cross SH, Mckie L, Keighren M, et al. Missense mutations in the human nanophthalmos gene TMEM98 cause retinal defects in the mouse. Invest Ophthalmol Vis Sci. 2019;60:2875-2887. https://doi.org/ 10.1167/iovs.18-25954PURPOSE. We previously found a dominant mutation, Rwhs, causing white spots on the retina accompanied by retinal folds. Here we identify the mutant gene to be Tmem98. In humans, mutations in the orthologous gene cause nanophthalmos. We modeled these mutations in mice and characterized the mutant eye phenotypes of these and Rwhs.METHODS. The Rwhs mutation was identified to be a missense mutation in Tmem98 by genetic mapping and sequencing. The human TMEM98 nanophthalmos missense mutations were made in the mouse gene by CRISPR-Cas9. Eyes were examined by indirect ophthalmoscopy and the retinas imaged using a retinal camera. Electroretinography was used to study retinal function. Histology, immunohistochemistry, and electron microscopy techniques were used to study adult eyes.RESULTS. An I135T mutation of Tmem98 causes the dominant Rwhs phenotype and is perinatally lethal when homozygous. Two dominant missense mutations of TMEM98, A193P and H196P, are associated with human nanophthalmos. In the mouse these mutations cause recessive retinal defects similar to the Rwhs phenotype, either alone or in combination with each other, but do not cause nanophthalmos. The retinal folds did not affect retinal function as assessed by electroretinography. Within the folds there was accumulation of disorganized outer segment material as demonstrated by immunohistochemistry and electron microscopy, and macrophages had infiltrated into these regions. CONCLUSIONS.Mutations in the mouse orthologue of the human nanophthalmos gene TMEM98 do not result in small eyes. Rather, there is localized disruption of the laminar structure of the photoreceptors.

show abstract

mentioning

confidence: 99%

Missense Mutations in the Human Nanophthalmos GeneTMEM98Cause Retinal Defects in the Mouse

Cross

McKie

Keighren

et al. 2019

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…Also, TMEM98 may confer chemoresistance of hepatocellular carcinoma through activation of the AKT pathway and deactivation of p53, suggesting its novel molecular target potential associated with intrinsic and acquired chemoresistance of hepatocellular carcinoma [ 26 ]. A missense mutation in this gene also resulted in Nanophthalmos 4 (NNO4) [ 17 , 27 , 28 ]. In adenocarcinoma, TMEM98's high expression leads to the worst prognosis of adenocarcinoma than other types of cancer [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of IL-8-mediated endothelial adhesion, VSMCs proliferation and migration by siRNA-TMEM98 suggests TMEM98's emerging role in atherosclerosis

Zhu

Cai

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Transmembrane protein 98 (TMEM98), known as a novel gene related to lung cancer, hepatocellular carcinoma, differentiation of T helper 1 cells and normal eye development, has no defined role reported in terms of atherosclerosis (AS). To investigate the potential involvement of TMEM98 during AS processes, its obvious secretion and expression has been initially characterized in hyperlipidemia patients’ serum and AS mice's serum respectively. We then explored the possible role of TMEM98 in the pathogenesis of AS in vitro. IL-8, a pro-atherogenesis cytokine, was used to induce the expression of TMEM98 in both endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Collectively, TMEM98 expression significantly increased in ECs and VSMCs, both induced by IL-8. Additionally, the adhesion ability of monocytes to ECs as well as the proliferation and migration of VSMCs were all decreased after siRNA-TMEM98 treatment. Furthermore, siRNA-TMEM98 dramatically inhibited the expression of ICAM-1 in ECs and the expression of p-AKT, p-GSK3β and Cyclin D1 from VSMCs, and AKT agonist partially restored the proliferation and migration of VSMC after siRNA-TMEM98 treatment. Taken together, siRNA-TMEM98 inhibits IL-8 mediated EC adhesion by down-regulating the expression of ICAM-1. Additionally, it also hinders the proliferation and migration of VSMCs through suppressing the AKT/GSK3β/Cyclin D1 signaling pathway. Our study provides sufficient evidence to support that TMEM98 could be a novel gene associated with AS for the first time.

show abstract

“…[5][6][7][8][9] Pedigree analyses have demonstrated inheritance of hyperopia as autosomal-dominant and autosomal-recessive traits. Several loci for high hyperopia have been mapped, including NNO1 (OMIM 600165) at chromosome 11p for autosomal-dominant nanophthalmos, 6 MFRP of NNO2 (OMIM 606227) at chromosome 11q23.3 for autosomal-recessive nanophthalmos, 10 NNO3 (OMIM 611897) at chromosome 2q11-q14 for autosomal-dominant congenital simple microphthalmia, 11 TMEM98 of NNO4 (OMIM 615949) at chromosome 17p12-q12 for autosomaldominant nanophthalmos, 12,13 and PRSS56 (OMIM 613858) at chromosome 2q37.1 for autosomal-recessive posterior microphthalmos. 14,15 Families with physiologic high hyperopia are not uncommon, but the loci or genes responsible for them are yet to be identified.…”

Section: Molecular Genetics Of Hyperopiamentioning

confidence: 99%

Genetics of Refraction and Myopia

Zhang

2015

Progress in Molecular Biology and Translational Science

Self Cite

View full text Add to dashboard Cite

Does the Association BetweenTMEM98and Nanophthalmos Require Further Confirmation?

Cited by 9 publications

References 7 publications

Missense Mutations in the Human Nanophthalmos GeneTMEM98Cause Retinal Defects in the Mouse

Missense Mutations in the Human Nanophthalmos GeneTMEM98Cause Retinal Defects in the Mouse

Inhibition of IL-8-mediated endothelial adhesion, VSMCs proliferation and migration by siRNA-TMEM98 suggests TMEM98's emerging role in atherosclerosis

Genetics of Refraction and Myopia

Contact Info

Product

Resources

About