Iranian
Biomedical Journal
Volume 24, Issue 4 (7-2020)
IBJ 2020, 24(4): 257-263 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Bushehri A, Zare-Abdollahi D, Hashemian H, Safavizadeh L, Effati J, Khorram Khorshid H R. Novel Bi-allelic PDE6C Variant Leads to Congenital Achromatopsia. IBJ 2020; 24 (4) :257-263
URL: http://ibj.pasteur.ac.ir/article-1-2998-en.html
URL: http://ibj.pasteur.ac.ir/article-1-2998-en.html
Ata Bushehri 
, Davood Zare-Abdollahi , Hesam Hashemian , Ladan Safavizadeh , Jalil Effati , Hamid Reza Khorram Khorshid
, Davood Zare-Abdollahi , Hesam Hashemian , Ladan Safavizadeh , Jalil Effati , Hamid Reza Khorram Khorshid
Abstract:
Background: The clinical phenotyping of patients with achromatopsia harboring variants in phosphordiesterase 6C (PDE6C) has poorly been described in the literature. PDE6C encodes the catalytic subunit of the cone phosphodiesterase, which hydrolyzes the cyclic guanosine monophosphate that proceeds with the hyperpolarization of photoreceptor cell membranes, as the final step of the phototransduction cascade. Methods: In the current study, two patients from a consanguineous family underwent full ophthalmologic examination and molecular investigations including WES. The impact of the variant on the functionality of the protein has been analyzed using in silico molecular modeling. Results: The patients identified with achromatopsia segregated a homozygous missense variant (c.C1775A:p.A592D) in PDE6C gene located on chromosome 10q23. Molecular modeling demonstrated that the variant would cause a protein conformational change and result in reduced phosphodiesterase activity. Conclusion: Our data extended the phenotypic spectrum of retinal disorders caused by PDE6C variants and provided new clinical and genetic information on achromatopsia.
Type of Study: Case Report |
Subject:
Molecular Genetics & Genomics
References
1. Sundaram V, Wilde C, Aboshiha J, Cowing J, Han C, Langlo CS, Chana R, Davidson AE, Sergouniotis PI, Bainbridge JW, Ali RR, Dubra A, Rubin G, Webster AR, Moore AT, Nardini M, Carroll J, Michaelides M. Retinal structure and function in achromatopsia: implications for gene therapy. Ophthalmology 2014; 121(1): 234-245. [DOI:10.1016/j.ophtha.2013.08.017]
2. Thiadens AA, Slingerland NW, Roosing S, van Schooneveld MJ, van Lith-Verhoeven JJ, van Moll-Ramirez N, van den Born LI, Hoyng CB, Cremers FP, Klaver CC. Genetic etiology and clinical consequences of complete and incomplete achromatopsia. Ophthalmology 2009; 116(10): 1984-1989. [DOI:10.1016/j.ophtha.2009.03.053]
3. Khan NW, Wissinger B, Kohl S, Sieving PA. CNGB3 achromatopsia with progressive loss of residual cone function and impaired rod-mediated function. Investigative ophthalmology and visual science 2007; 48(8): 3864-3871. [DOI:10.1167/iovs.06-1521]
4. Uzunov P, Weiss B. Separation of multiple molecular forms of cyclic adenosine-3′,5′-monophosphate phosphodiesterase in rat cerebellum by polyacrylamide gel electrophoresis. Biochimica et biophysica acta 1972; 284(1): 220-226. [DOI:10.1016/0005-2744(72)90060-5]
5. Zhang X, Cote RH. cGMP signaling in vertebrate retinal photoreceptor cells. Frontiers in bioscience 2005; 10: 1191-1204. [DOI:10.2741/1612]
6. Thiadens AA, den Hollander AI, Roosing S, Nabuurs SB, Zekveld-Vroon RC, Collin RW, De Baere E, Koenekoop RK, van Schooneveld MJ, Strom TM, van Lith-Verhoeven JJ, Lotery AJ, van Moll-Ramirez N, Leroy BP, van den Born LI, Hoyng CB, Cremers FP, Klaver CC. Homozygosity mapping reveals PDE6C mutations in patients with early-onset cone photoreceptor disorders. The American journal of human genetics 2009; 85(2): 240-247. [DOI:10.1016/j.ajhg.2009.06.016]
7. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in medicine 2015; 17(5): 405-424. [DOI:10.1038/gim.2015.30]
8. Barren B, Gakhar L, Muradov H, Boyd KK, Ramaswamy S, Artemyev NO. Structural basis of phosphodiesterase 6 inhibition by the C‐terminal region of the γ‐subunit. The EMBO journal 2009; 28(22): 3613-3622. [DOI:10.1038/emboj.2009.284]
9. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. UCSF Chimera-a visualization system for exploratory research and analysis. Journal of computational chemistry 2004; 25(13): 1605-1612. [DOI:10.1002/jcc.20084]
10. Greenberg JP, Sherman J, Zweifel SA, Chen RW, Duncker T, Kohl S, Baumann B, Wissinger B, Yannuzzi LA, Tsang SH. Spectral-domain optical coherence tomography staging and autofluorescence imaging in achromatopsia. JAMA ophthalmology 2014; 132(4): 437-445. [DOI:10.1001/jamaophthalmol.2013.7987]
11. Letunic I, Bork P. 20 years of the SMART protein domain annotation resource. Nucleic acids research 2017; 46(D1): D493-D496. [DOI:10.1093/nar/gkx922]
12. Gopalakrishna KN, Boyd K, Artemyev NO. Mechanisms of mutant PDE6 proteins underlying retinal diseases. Cellular signaling 2017; 37: 74-80. [DOI:10.1016/j.cellsig.2017.06.002]
13. Katagiri S, Hayashi T, Yoshitake K, Sergeev Y, Akahori M, Furuno M, Nishino J, Ikeo K, Tsunoda K, Tsuneoka H, Iwata T. Congenital achromatopsia and macular atrophy caused by a novel recessive PDE6C mutation (p. E591K). Ophthalmic genetics 2015; 36(2): 137-144. [DOI:10.3109/13816810.2014.991932]
14. Gopalakrishna KN, Boyad K, Yadav RP, Artemyev NO. Aryl hydrocarbon receptor-interacting protein-like 1 is an obligate chaperone of phosphodiesterase 6 and is assisted by the γ-subunit of its client. Journal of biological chemistry 2016; 291(31): 16282-16291. [DOI:10.1074/jbc.M116.737593]
15. Iribarne M, Masai I. Neurotoxicity of cGMP in the vertebrate retina: From the initial research on rd mutant mice to zebrafish genetic approaches. Journal of neurogenetics 2017; 31(3): 88-101. [DOI:10.1080/01677063.2017.1358268]
16. Chang B, Grau T, Dangel S, Hurd R, Jurklies B, Sener EC, Andreasson S, Dollfus H, Baumann B, Bolz S, Artemyev N, Kohl S, Heckenlively J, Wissinger B. Proceedings of the National Academy of Sciences USA 2009; 106(46): 19581-19586. [DOI:10.1073/pnas.0907720106]
17. Weisschuh N, Stingl K, Audo I, Biskup S, Bocquet B, Branham K, Burstedt MS, De Baere E, De Vries MJ, Golovleva I, Green A, Heckenlively J, Leroy BP, Meunier I, Traboulsi E, Wissinger B, Kohl S. Mutations in the gene PDE6C encoding the catalytic subunit of the cone photoreceptor phosphodiesterase in patients with achromatopsia. Human mutation 2018; 39(10): 1366-1371. [DOI:10.1002/humu.23606]
18. Zhang L, Zhang X, Zhang G, Pang CP, Leung YF, Zhang M, Zhong W. Expression profiling of the retina of pde6c, a zebrafish model of retinal degeneration. Scientific data 2017; 4: Article no. 70182. [DOI:10.1038/sdata.2017.182]
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
IBJ is a member of Committee on Publication Ethics (COPE)
and follows its guidelines |
The articles of this journal are licensed under
a Creative Commons Attribution-NonDerivatives 4.0 International License. .png) |
 IBJ is owned and published by Pasteur Institute of Iran |