A new perspective on the genetics of keratoconus: why have we not been more successful?
作者： Hanne Valgaeren , Carina Koppen , Guy Van Camp
DOI: 10.1080/13816810.2017.1393831
关键词:
摘要: Twin studies and family suggest an important genetic basis for keratoconus (KC). Involvement association of several genes with the disease has been reported. Additionally, associated central corneal thickness (CCT) curvature (CC) via genome-wide (GWAS), also potentially underlie KC. Although a long list reported KC, evidence pathogenic role most remains limited. Furthermore, if involvement in KC development can be proven, they only account limited number patients. VSX1, ZNF469, SOD1, miR184 have frequently investigated, but mutations indisputably abnormalities. For three other genes, analysis minor allele frequencies (MAF) public databases argues against variants. remainder variants, functional is needed to prove their contribution pathogenesis. Despite large amount studies, clear results remain rare. A possible explanation cumbersome gene-identification that defects underlying are located regions understudied (such as non-coding regions) or not monogenic (= one gene effect size) initially considered. Since many applied research strategies identify mutations, variants smaller sizes might lead more progress research.
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sci-hub.se 参考文章(136)
Ariela Gordon-Shaag, Michel Millodot, Igor Kaiserman, Tzahi Sela, Guy Barnett Itzhaki, Yaffa Zerbib, Efrat Matityahu, Shira Shkedi, Svetlana Miroshnichenko, Einat Shneor, Risk factors for keratoconus in Israel: a case-control study. Ophthalmic and Physiological Optics. ,vol. 35, pp. 673- 681 ,(2015) , 10.1111/OPO.12237
, A global reference for human genetic variation. Nature. ,vol. 526, pp. 68- 74 ,(2015) , 10.1038/NATURE15393
Ali M. Hellani, Abdulrahman M. Al-Muammar, Hatem Kalantan, Khaled K. Abu-Amero, Sameer M. Al Mansouri, High-resolution analysis of DNA copy number alterations in patients with isolated sporadic keratoconus. Molecular Vision. ,vol. 17, pp. 822- 826 ,(2011)
Judith Lechner, Louise F Porter, Aine Rice, Veronique Vitart, David J Armstrong, Daniel F Schorderet, Francis L Munier, Alan F Wright, Chris F Inglehearn, Graeme C Black, David A Simpson, Forbes Manson, Colin E Willoughby, None, Enrichment of pathogenic alleles in the brittle cornea gene, ZNF469, in keratoconus Human Molecular Genetics. ,vol. 23, pp. 5527- 5535 ,(2014) , 10.1093/HMG/DDU253
Gabriel Cuellar-Partida, Henriët Springelkamp, Sionne E. M. Lucas, Seyhan Yazar, Alex W. Hewitt, Adriana I. Iglesias, Grant W. Montgomery, Nicholas G. Martin, Craig E. Pennell, Elisabeth M. van Leeuwen, Virginie J. M. Verhoeven, Albert Hofman, André G. Uitterlinden, Wishal D. Ramdas, Roger. C. W. Wolfs, Johannes R. Vingerling, Matthew A. Brown, Richard A. Mills, Jamie E. Craig, Caroline C. W. Klaver, Cornelia M. van Duijn, Kathryn P. Burdon, Stuart MacGregor, David A. Mackey, WNT10A exonic variant increases the risk of keratoconus by decreasing corneal thickness Human Molecular Genetics. ,vol. 24, pp. 5060- 5068 ,(2015) , 10.1093/HMG/DDV211
Reza Raoofian, Samira Saee-Rad, Mohammad Reza Noori-Daloii, Farhad Rezvan, Mohammad Miraftab, Ghasem Fakhraie, Wayne Greene, Hassan Hashemi, Mansour Heidari, Fatemeh Jafari, Morteza Hashemzadeh Chaleshtori, Mutation analysis of VSX1 and SOD1 in Iranian patients with keratoconus Molecular Vision. ,vol. 17, pp. 3128- 3136 ,(2011)
Yi Lu, Veronique Vitart, Kathryn P Burdon, Chiea Chuen Khor, Yelena Bykhovskaya, Alireza Mirshahi, Alex W Hewitt, Demelza Koehn, Pirro G Hysi, Wishal D Ramdas, Tanja Zeller, Eranga N Vithana, Belinda K Cornes, Wan-Ting Tay, E Shyong Tai, Ching-Yu Cheng, Jianjun Liu, Jia-Nee Foo, Seang Mei Saw, Gudmar Thorleifsson, Kari Stefansson, David P Dimasi, Richard A Mills, Jenny Mountain, Wei Ang, René Hoehn, Virginie JM Verhoeven, Franz Grus, Roger Wolfs, Raphaële Castagne, Karl J Lackner, Henriët Springelkamp, Jian Yang, Fridbert Jonasson, Dexter YL Leung, Li J Chen, Clement CY Tham, Igor Rudan, Zoran Vatavuk, Caroline Hayward, Jane Gibson, Angela J Cree, Alex MacLeod, Sarah Ennis, Ozren Polasek, Harry Campbell, James F Wilson, Ananth C Viswanathan, Brian Fleck, Xiaohui Li, David Siscovick, Kent D Taylor, Jerome I Rotter, Seyhan Yazar, Megan Ulmer, Jun Li, Brian L Yaspan, Ayse B Ozel, Julia E Richards, Sayoko E Moroi, Jonathan L Haines, Jae H Kang, Louis R Pasquale, R Rand Allingham, Allison Ashley-Koch, NEIGHBOR Consortium, Paul Mitchell, Jie Jin Wang, Alan F Wright, Craig Pennell, Timothy D Spector, Terri L Young, Caroline CW Klaver, Nicholas G Martin, Grant W Montgomery, Michael G Anderson, Tin Aung, Colin E Willoughby, Janey L Wiggs, Chi P Pang, Unnur Thorsteinsdottir, Andrew J Lotery, Christopher J Hammond, Cornelia M van Duijn, Michael A Hauser, Yaron S Rabinowitz, Norbert Pfeiffer, David A Mackey, Jamie E Craig, Stuart Macgregor, Tien Y Wong, None, Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus. Nature Genetics. ,vol. 45, pp. 155- 163 ,(2013) , 10.1038/NG.2506
K.H. Weed, C.J. MacEwen, C.N.J. McGhee, The variable expression of keratoconus within monozygotic twins: Dundee University Scottish Keratoconus Study (DUSKS) Contact Lens and Anterior Eye. ,vol. 29, pp. 123- 126 ,(2006) , 10.1016/J.CLAE.2006.03.003
A Shearer, Diana L Kolbe, Hela Azaiez, Christina M Sloan, Kathy L Frees, Amy E Weaver, Erika T Clark, Carla J Nishimura, E Black-Ziegelbein, Richard J H Smith, Copy number variants are a common cause of non-syndromic hearing loss Genome Medicine. ,vol. 6, pp. 37- 37 ,(2014) , 10.1186/GM554
Geert Vandeweyer, R Frank Kooy, Detection and interpretation of genomic structural variation in health and disease Expert Review of Molecular Diagnostics. ,vol. 13, pp. 61- 82 ,(2013) , 10.1586/ERM.12.119