Disease Progression in Autosomal Dominant Cone-rod Dystrophy Caused by a Novel Mutation (D100G) in the GUCA1A Gene

Overview

Journal Doc Ophthalmol

Specialty Ophthalmology

Date 2013 Dec 20

PMID 24352742

Citations 21

Authors

Eva Nong

Winston Lee

Joanna E Merriam

Rando Allikmets

Stephen H Tsang

Affiliations

Soon will be listed here.

Abstract

Purpose: To document longitudinal fundus autofluorescence (FAF) and electroretinogram (ERG) findings in a family with cone-rod dystrophy (CRD) caused by a novel missense mutation (D100G) in the GUCA1A gene.

Methods: Observational case series.

Results: Three family members 26-49 years old underwent complete clinical examinations. In all patients, funduscopic findings showed intraretinal pigment migration, loss of neurosensory retinal pigment epithelium, and macular atrophy. FAF imaging revealed the presence of a progressive hyperautofluorescent ring around a hypoautofluorescent center corresponding to macular atrophy. Full-field ERGs showed a more severe loss of cone than rod function in each patient. Thirty-hertz flicker responses fell far below normal limits. Longitudinal FAF and ERG findings in one patient suggested progressive CRD. Two more advanced patients exhibited reduced rod response consistent with disease stage. Direct sequencing of the GUCA1A gene revealed a new missense mutation, p.Asp100Gly (D100G), in each patient.

Conclusion: Patients with autosomal dominant CRD caused by a D100G mutation in GUCA1A exhibit progressive vision loss early within the first decade of life identifiable by distinct ERG characteristics and subsequent genetic testing.

Citing Articles

Structural basis of retinal membrane guanylate cyclase regulation by GCAP1 and RD3.

Ames J Front Mol Neurosci. 2022; 15:988142.

PMID: 36157073 PMC: 9493048. DOI: 10.3389/fnmol.2022.988142.

The Clinical Spectrum and Disease Course of DRAM2 Retinopathy.

Krasovec T, Volk M, Sustar Habjan M, Hawlina M, Vidovic Valentincic N, Fakin A Int J Mol Sci. 2022; 23(13).

PMID: 35806404 PMC: 9266529. DOI: 10.3390/ijms23137398.

Retinal Proteomic Analysis in a Mouse Model of Endotoxin-Induced Uveitis Using Data-Independent Acquisition-Based Mass Spectrometry.

Zhang J, Wu J, Lu D, To C, Lam T, Lin B Int J Mol Sci. 2022; 23(12).

PMID: 35742911 PMC: 9223489. DOI: 10.3390/ijms23126464.

Molecular Properties of Human Guanylate Cyclase-Activating Protein 3 (GCAP3) and Its Possible Association with Retinitis Pigmentosa.

Avesani A, Bielefeld L, Weisschuh N, Marino V, Mazzola P, Stingl K Int J Mol Sci. 2022; 23(6).

PMID: 35328663 PMC: 8948881. DOI: 10.3390/ijms23063240.

Structural Insights into Retinal Guanylate Cyclase Activator Proteins (GCAPs).

Ames J Int J Mol Sci. 2021; 22(16).

PMID: 34445435 PMC: 8395740. DOI: 10.3390/ijms22168731.

References

Perrault I, Rozet J, Gerber S, Ghazi I, Ducroq D, Souied E . Spectrum of retGC1 mutations in Leber's congenital amaurosis. Eur J Hum Genet. 2000; 8(8):578-82. DOI: 10.1038/sj.ejhg.5200503. View

Michaelides M, Wilkie S, Jenkins S, Holder G, Hunt D, Moore A . Mutation in the gene GUCA1A, encoding guanylate cyclase-activating protein 1, causes cone, cone-rod, and macular dystrophy. Ophthalmology. 2005; 112(8):1442-7. DOI: 10.1016/j.ophtha.2005.02.024. View

Gal A, Orth U, Baehr W, Schwinger E, Rosenberg T . Heterozygous missense mutation in the rod cGMP phosphodiesterase beta-subunit gene in autosomal dominant stationary night blindness. Nat Genet. 1994; 7(4):551. DOI: 10.1038/ng0894-551a. View

Kachi S, Nishizawa Y, Olshevskaya E, Yamazaki A, Miyake Y, Wakabayashi T . Detailed localization of photoreceptor guanylate cyclase activating protein-1 and -2 in mammalian retinas using light and electron microscopy. Exp Eye Res. 1999; 68(4):465-73. DOI: 10.1006/exer.1998.0629. View

Tsang S, Tsui I, Chou C, Zernant J, Haamer E, Iranmanesh R . A novel mutation and phenotypes in phosphodiesterase 6 deficiency. Am J Ophthalmol. 2008; 146(5):780-8. PMC: 2593460. DOI: 10.1016/j.ajo.2008.06.017. View

Johnson S, Halford S, Morris A, Patel R, Wilkie S, Hardcastle A . Genomic organisation and alternative splicing of human RIM1, a gene implicated in autosomal dominant cone-rod dystrophy (CORD7). Genomics. 2003; 81(3):304-14. DOI: 10.1016/s0888-7543(03)00010-7. View

Payne A, Morris A, Downes S, Johnson S, Bird A, Moore A . Clustering and frequency of mutations in the retinal guanylate cyclase (GUCY2D) gene in patients with dominant cone-rod dystrophies. J Med Genet. 2001; 38(9):611-4. PMC: 1734946. DOI: 10.1136/jmg.38.9.611. View

Sancho-Pelluz J, Tosi J, Hsu C, Lee F, Wolpert K, Tabacaru M . Mice with a D190N mutation in the gene encoding rhodopsin: a model for human autosomal-dominant retinitis pigmentosa. Mol Med. 2012; 18:549-55. PMC: 3388123. DOI: 10.2119/molmed.2011.00475. View

Sohocki M, Daiger S, Bowne S, Rodriquez J, Northrup H, Heckenlively J . Prevalence of mutations causing retinitis pigmentosa and other inherited retinopathies. Hum Mutat. 2001; 17(1):42-51. PMC: 2585107. DOI: 10.1002/1098-1004(2001)17:1<42::AID-HUMU5>3.0.CO;2-K. View

10.

Yang R, Foster D, Garbers D, Fulle H . Two membrane forms of guanylyl cyclase found in the eye. Proc Natl Acad Sci U S A. 1995; 92(2):602-6. PMC: 42790. DOI: 10.1073/pnas.92.2.602. View

11.

Abid A, Ismail M, Mehdi S, Khaliq S . Identification of novel mutations in the SEMA4A gene associated with retinal degenerative diseases. J Med Genet. 2005; 43(4):378-81. PMC: 2563224. DOI: 10.1136/jmg.2005.035055. View

12.

Nishiguchi K, Sokal I, Yang L, Roychowdhury N, Palczewski K, Berson E . A novel mutation (I143NT) in guanylate cyclase-activating protein 1 (GCAP1) associated with autosomal dominant cone degeneration. Invest Ophthalmol Vis Sci. 2004; 45(11):3863-70. PMC: 1475955. DOI: 10.1167/iovs.04-0590. View

13.

Bovolenta P, Cisneros E . Retinitis pigmentosa: cone photoreceptors starving to death. Nat Neurosci. 2008; 12(1):5-6. DOI: 10.1038/nn0109-5. View

14.

Polans A, Baehr W, Palczewski K . Turned on by Ca2+! The physiology and pathology of Ca(2+)-binding proteins in the retina. Trends Neurosci. 1996; 19(12):547-54. DOI: 10.1016/s0166-2236(96)10059-x. View

15.

Katz M, Drea C, Eldred G, Hess H, Robison Jr W . Influence of early photoreceptor degeneration on lipofuscin in the retinal pigment epithelium. Exp Eye Res. 1986; 43(4):561-73. DOI: 10.1016/s0014-4835(86)80023-9. View

16.

Krill A, Deutman A, Fishman M . The cone degenerations. Doc Ophthalmol. 1973; 35(1):1-80. DOI: 10.1007/BF00234530. View

17.

Marmor M, Fulton A, Holder G, Miyake Y, Brigell M, Bach M . ISCEV Standard for full-field clinical electroretinography (2008 update). Doc Ophthalmol. 2008; 118(1):69-77. DOI: 10.1007/s10633-008-9155-4. View

18.

Kobayashi A, Higashide T, HAMASAKI D, Kubota S, Sakuma H, An W . HRG4 (UNC119) mutation found in cone-rod dystrophy causes retinal degeneration in a transgenic model. Invest Ophthalmol Vis Sci. 2000; 41(11):3268-77. View

19.

Perrault I, Rozet J, Calvas P, Gerber S, Camuzat A, Dollfus H . Retinal-specific guanylate cyclase gene mutations in Leber's congenital amaurosis. Nat Genet. 1996; 14(4):461-4. DOI: 10.1038/ng1296-461. View

20.

Hamel C . Cone rod dystrophies. Orphanet J Rare Dis. 2007; 2:7. PMC: 1808442. DOI: 10.1186/1750-1172-2-7. View