IMPORTANCE: Mutations in CNGA3 are the most common cause of achromatopsia and cone-rod dystrophies. OBJECTIVE: To identify CNGA3 mutations in patients with cone dystrophies or Leber congenital amaurosis. DESIGN, SETTING, AND PARTICIPANTS: Clinical data and genomic DNA in 267 Chinese probands from 138 families with cone dystrophies and 129 families with Leber congenital amaurosis collected at the Zhongshan Ophthalmic Center, Guangzhou, China. MAIN OUTCOMES AND MEASURES: Variants in CNGA3 and associated phenotypes, assessed by Sanger sequencing of CNGA3, bioinformatics of variants, and segregation analysis. RESULTS: Homozygous or compound heterozygous mutations in CNGA3, including 26 novel and 13 known mutations, were identified in 46 probands from 138 families with cone dystrophies, but none were found in any of the probands from 129 families with Leber congenital amaurosis. The 46 probands with CNGA3 mutations could be further classified as likely having achromatopsia (18 probands) and cone-rod dystrophies (28 probands) based on electroretinographic recordings. Analysis of family members in 17 of 46 families demonstrated good segregation of the disease with the CNGA3 mutations. CONCLUSIONS AND RELEVANCE: To our knowledge, this study is the first systemic analysis of CNGA3 in Chinese patients and expands the mutational spectrum and associated phenotypes. Our results suggest that CNGA3 mutations are a common cause of cone-rod dystrophies and achromatopsia in the Chinese population. These data indicate that CNGA3-associated cone dystrophies may be a common form of early-onset severe retinal dystrophies. Therapeutic potential such as gene therapy targeting this gene may benefit some children with early-onset severe retinal dystrophies.
IMPORTANCE: Mutations in CNGA3 are the most common cause of achromatopsia and cone-rod dystrophies. OBJECTIVE: To identify CNGA3 mutations in patients with cone dystrophies or Leber congenital amaurosis. DESIGN, SETTING, AND PARTICIPANTS: Clinical data and genomic DNA in 267 Chinese probands from 138 families with cone dystrophies and 129 families with Leber congenital amaurosis collected at the Zhongshan Ophthalmic Center, Guangzhou, China. MAIN OUTCOMES AND MEASURES: Variants in CNGA3 and associated phenotypes, assessed by Sanger sequencing of CNGA3, bioinformatics of variants, and segregation analysis. RESULTS: Homozygous or compound heterozygous mutations in CNGA3, including 26 novel and 13 known mutations, were identified in 46 probands from 138 families with cone dystrophies, but none were found in any of the probands from 129 families with Leber congenital amaurosis. The 46 probands with CNGA3 mutations could be further classified as likely having achromatopsia (18 probands) and cone-rod dystrophies (28 probands) based on electroretinographic recordings. Analysis of family members in 17 of 46 families demonstrated good segregation of the disease with the CNGA3 mutations. CONCLUSIONS AND RELEVANCE: To our knowledge, this study is the first systemic analysis of CNGA3 in Chinese patients and expands the mutational spectrum and associated phenotypes. Our results suggest that CNGA3 mutations are a common cause of cone-rod dystrophies and achromatopsia in the Chinese population. These data indicate that CNGA3-associated cone dystrophies may be a common form of early-onset severe retinal dystrophies. Therapeutic potential such as gene therapy targeting this gene may benefit some children with early-onset severe retinal dystrophies.
Authors: Markus Burkard; Susanne Kohl; Timm Krätzig; Naoyuki Tanimoto; Christina Brennenstuhl; Anne E Bausch; Katrin Junger; Peggy Reuter; Vithiyanjali Sothilingam; Susanne C Beck; Gesine Huber; Xi-Qin Ding; Anja K Mayer; Britta Baumann; Nicole Weisschuh; Ditta Zobor; Gesa-Astrid Hahn; Ulrich Kellner; Sascha Venturelli; Elvir Becirovic; Peter Charbel Issa; Robert K Koenekoop; Günther Rudolph; John Heckenlively; Paul Sieving; Richard G Weleber; Christian Hamel; Xiangang Zong; Martin Biel; Robert Lukowski; Matthias W Seeliger; Stylianos Michalakis; Bernd Wissinger; Peter Ruth Journal: J Clin Invest Date: 2018-11-12 Impact factor: 19.456
Authors: Muhammad Ansar; Regie Lyn P Santos-Cortez; Muhammad Arif Nadeem Saqib; Fareeha Zulfiqar; Kwanghyuk Lee; Naeem Mahmood Ashraf; Ehsan Ullah; Xin Wang; Sundus Sajid; Falak Sher Khan; Muhammad Amin-ud-Din; Joshua D Smith; Jay Shendure; Michael J Bamshad; Deborah A Nickerson; Abdul Hameed; Saima Riazuddin; Zubair M Ahmed; Wasim Ahmad; Suzanne M Leal Journal: Hum Genet Date: 2015-06-11 Impact factor: 4.132