OBJECTIVE: To investigate whether the major achromatopsia genes (CNGA3 and CNGB3) play a role in the cause of progressive cone dystrophy (CD). DESIGN: Prospective multicenter study. PARTICIPANTS: Probands (N = 60) with autosomal recessive (ar) CD from various ophthalmogenetic clinics in The Netherlands. METHODS: All available ophthalmologic data from the arCD probands were registered from medical charts and updated by an additional ophthalmologic examination. Mutations in the CNGA3 and CNGB3 genes were analyzed by direct sequencing. MAIN OUTCOME MEASURES: CNGA3 and CNGB3 mutations and clinical course in arCD probands. RESULTS: In 3 arCD probands (3/60; 5%) we found 2 mutations in the CNGB3 gene. Two of these probands had compound heterozygous mutations (p.R296YfsX9/p.R274VfsX12 and p.R296YfsX9/c.991-3T>g). The third proband revealed homozygous missense mutations (p.R403Q) with 2 additional variants in the CNGA3 gene (p.E228K and p.V266M). These probands did not have a congenital nystagmus, but had a progressive deterioration of visual acuity, color vision, and photopic electroretinogram, with onset in the second decade. In 6 other unrelated probands, we found 6 different heterozygous amino acid changes in the CNGA3 (N = 4) and CNGB3 (N = 2) gene. CONCLUSIONS: The CNGB3 gene accounts for a small fraction of the later onset progressive form of cone photoreceptor disorders, and CNGA3 may have an additive causative effect. Our data indicate that these genes are involved in a broader spectrum of cone dysfunction, and it remains intriguing why initial cone function can be spared despite similar gene defects. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
OBJECTIVE: To investigate whether the major achromatopsia genes (CNGA3 and CNGB3) play a role in the cause of progressive cone dystrophy (CD). DESIGN: Prospective multicenter study. PARTICIPANTS: Probands (N = 60) with autosomal recessive (ar) CD from various ophthalmogenetic clinics in The Netherlands. METHODS: All available ophthalmologic data from the arCD probands were registered from medical charts and updated by an additional ophthalmologic examination. Mutations in the CNGA3 and CNGB3 genes were analyzed by direct sequencing. MAIN OUTCOME MEASURES: CNGA3 and CNGB3 mutations and clinical course in arCD probands. RESULTS: In 3 arCD probands (3/60; 5%) we found 2 mutations in the CNGB3 gene. Two of these probands had compound heterozygous mutations (p.R296YfsX9/p.R274VfsX12 and p.R296YfsX9/c.991-3T>g). The third proband revealed homozygous missense mutations (p.R403Q) with 2 additional variants in the CNGA3 gene (p.E228K and p.V266M). These probands did not have a congenital nystagmus, but had a progressive deterioration of visual acuity, color vision, and photopic electroretinogram, with onset in the second decade. In 6 other unrelated probands, we found 6 different heterozygous amino acid changes in the CNGA3 (N = 4) and CNGB3 (N = 2) gene. CONCLUSIONS: The CNGB3 gene accounts for a small fraction of the later onset progressive form of cone photoreceptor disorders, and CNGA3 may have an additive causative effect. Our data indicate that these genes are involved in a broader spectrum of cone dysfunction, and it remains intriguing why initial cone function can be spared despite similar gene defects. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Authors: Jessica C Gardner; Tom R Webb; Naheed Kanuga; Anthony G Robson; Graham E Holder; Andrew Stockman; Caterina Ripamonti; Neil D Ebenezer; Olufunmilola Ogun; Sophie Devery; Genevieve A Wright; Eamonn R Maher; Michael E Cheetham; Anthony T Moore; Michel Michaelides; Alison J Hardcastle Journal: Am J Hum Genet Date: 2010-06-24 Impact factor: 11.025
Authors: Tanja Grau; Nikolai O Artemyev; Thomas Rosenberg; Hélène Dollfus; Olav H Haugen; E Cumhur Sener; Bernhard Jurklies; Sten Andreasson; Christoph Kernstock; Michael Larsen; Eberhart Zrenner; Bernd Wissinger; Susanne Kohl Journal: Hum Mol Genet Date: 2010-12-01 Impact factor: 6.150
Authors: Ebrahim Jafarzadehpur; Hassan Hashemi; Mohammad Hassan Emamian; Mehdi Khabazkhoob; Shiva Mehravaran; Mohammad Shariati; Akbar Fotouhi Journal: Int Ophthalmol Date: 2014-02-14 Impact factor: 2.031
Authors: Maleeha Azam; Rob W J Collin; Syed Tahir Abbas Shah; Aftab Ali Shah; Muhammad Imran Khan; Alamdar Hussain; Ahmed Sadeque; Tim M Strom; Alberta A H J Thiadens; Susanne Roosing; Anneke I den Hollander; Frans P M Cremers; Raheel Qamar Journal: Mol Vis Date: 2010-04-29 Impact factor: 2.367
Authors: Rong Chen; Lisong Shi; Jörg Hakenberg; Brian Naughton; Pamela Sklar; Jianguo Zhang; Hanlin Zhou; Lifeng Tian; Om Prakash; Mathieu Lemire; Patrick Sleiman; Wei-Yi Cheng; Wanting Chen; Hardik Shah; Yulan Shen; Menachem Fromer; Larsson Omberg; Matthew A Deardorff; Elaine Zackai; Jason R Bobe; Elissa Levin; Thomas J Hudson; Leif Groop; Jun Wang; Hakon Hakonarson; Anne Wojcicki; George A Diaz; Lisa Edelmann; Eric E Schadt; Stephen H Friend Journal: Nat Biotechnol Date: 2016-04-11 Impact factor: 54.908