Kazuki Kuniyoshi1, Sanae Muraki-Oda2, Hisao Ueyama3, Futoshi Toyoda4, Hiroyuki Sakuramoto5, Hisakazu Ogita3, Motohiro Irifune5,6, Shuji Yamamoto7,8, Akira Nakao5, Kazushige Tsunoda9, Takeshi Iwata10, Masahito Ohji2, Yoshikazu Shimomura5. 1. Department of Ophthalmology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, 589-8911, Japan. kuniyoshi-kazuki@umin.net. 2. Department of Ophthalmology, Shiga University of Medical Science, Otsu, Japan. 3. Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Japan. 4. Department of Physiology, Shiga University of Medical Science, Otsu, Japan. 5. Department of Ophthalmology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, 589-8911, Japan. 6. Irifune Eye Clinic, Izumi, Japan. 7. Jin Eye Clinic, Nishinomiya, Japan. 8. Department of Ophthalmology, Graduate School of Medicine, Osaka University, Suita, Japan. 9. Laboratory of Visual Physiology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan. 10. Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Abstract
PURPOSE: To present the characteristics and pathology of a patient with congenital achromatopsia. PATIENT AND METHODS: The patient was a 22-year-old Japanese woman who was 8 years old when she first visited our clinic. Comprehensive ophthalmic examinations including visual acuity measurements, perimetry, optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, electroretinography (ERG), and color vision tests were performed. Her genomic DNA was used as the template for the amplification of exons of five candidate genes for achromatopsia; CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H, and the amplified products were sequenced. A missense mutation, found in the CNGA3, was studied both electrophysiologically and biochemically. RESULTS: Her phenotype was typical of congenital complete achromatopsia. She was followed for 14 years, and her vision and fundus findings were stable. However, the scotopic ERG b-waves at age 22 were smaller than those at age 8, and her FAF images showed increased autofluorescence in both maculae. Genetic examinations revealed combined heterozygous mutations of c.997_998delGA and p.M424V in the CNGA3 gene. The homomeric channel consisting of the CNGA3 subunit with the p.M424V mutation had a weak cGMP-activated current in patch-clamp recordings. In heterologous expression analyses, the expression at the cell surface of the mutant CNGA3 subunit was about 28 % of the wild type. CONCLUSIONS: The two novel mutations found in the CNGA3 gene, c.997_998delGA and p.M424V, can cause complete achromatopsia. The vision of the patient was stationary until the third decade of life although the FAF was altered at the age of 22 years.
PURPOSE: To present the characteristics and pathology of a patient with congenital achromatopsia. PATIENT AND METHODS: The patient was a 22-year-old Japanese woman who was 8 years old when she first visited our clinic. Comprehensive ophthalmic examinations including visual acuity measurements, perimetry, optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, electroretinography (ERG), and color vision tests were performed. Her genomic DNA was used as the template for the amplification of exons of five candidate genes for achromatopsia; CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H, and the amplified products were sequenced. A missense mutation, found in the CNGA3, was studied both electrophysiologically and biochemically. RESULTS: Her phenotype was typical of congenital complete achromatopsia. She was followed for 14 years, and her vision and fundus findings were stable. However, the scotopic ERG b-waves at age 22 were smaller than those at age 8, and her FAF images showed increased autofluorescence in both maculae. Genetic examinations revealed combined heterozygous mutations of c.997_998delGA and p.M424V in the CNGA3 gene. The homomeric channel consisting of the CNGA3 subunit with the p.M424V mutation had a weak cGMP-activated current in patch-clamp recordings. In heterologous expression analyses, the expression at the cell surface of the mutant CNGA3 subunit was about 28 % of the wild type. CONCLUSIONS: The two novel mutations found in the CNGA3 gene, c.997_998delGA and p.M424V, can cause complete achromatopsia. The vision of the patient was stationary until the third decade of life although the FAF was altered at the age of 22 years.
Authors: Susanne Kohl; Frauke Coppieters; Françoise Meire; Simone Schaich; Susanne Roosing; Christina Brennenstuhl; Sylvia Bolz; Maria M van Genderen; Frans C C Riemslag; Robert Lukowski; Anneke I den Hollander; Frans P M Cremers; Elfride De Baere; Carel B Hoyng; Bernd Wissinger Journal: Am J Hum Genet Date: 2012-08-16 Impact factor: 11.025
Authors: Alberta A H J Thiadens; Anneke I den Hollander; Susanne Roosing; Sander B Nabuurs; Renate C Zekveld-Vroon; Rob W J Collin; Elfride De Baere; Robert K Koenekoop; Mary J van Schooneveld; Tim M Strom; Janneke J C van Lith-Verhoeven; Andrew J Lotery; Norka van Moll-Ramirez; Bart P Leroy; L Ingeborgh van den Born; Carel B Hoyng; Frans P M Cremers; Caroline C W Klaver Journal: Am J Hum Genet Date: 2009-07-16 Impact factor: 11.025
Authors: Abigail T Fahim; Naheed W Khan; Sarwar Zahid; Ira H Schachar; Kari Branham; Susanne Kohl; Bernd Wissinger; Victor M Elner; John R Heckenlively; Thiran Jayasundera Journal: Am J Ophthalmol Date: 2013-08-20 Impact factor: 5.258