title: Novel mutations in the gene for α-subunit of retinal cone cyclic nucleotide-gated channels in a Japanese patient with congenital achromatopsia.
abstract: OBJECTIVE
  To present the characteristics and pathology of a patient with congenital achromatopsia.
  
  
  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.affiliation: Department of Ophthalmology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, 589-8911, Japan. kuniyoshi-kazuki@umin.net.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kuniyoshi
authors.affiliation: Department of Ophthalmology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Sanae
authors.initials: S
authors.lastname: Muraki-Oda
authors.affiliation: Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ueyama
authors.affiliation: Department of Physiology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Toyoda
authors.affiliation: Department of Ophthalmology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, 589-8911, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sakuramoto
authors.affiliation: Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Ogita
authors.affiliation: Department of Ophthalmology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, 589-8911, Japan.|Irifune Eye Clinic, Izumi, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Irifune
authors.affiliation: Jin Eye Clinic, Nishinomiya, Japan.|Department of Ophthalmology, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Department of Ophthalmology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, 589-8911, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakao
authors.affiliation: Laboratory of Visual Physiology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Tsunoda
authors.affiliation: Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwata
authors.affiliation: Department of Ophthalmology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Ohji
authors.affiliation: Department of Ophthalmology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, 589-8911, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Shimomura
mesh_terms: D003117:Color Vision Defects / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005260:Female; D005838:Genotype; D006801:Humans; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017949:Retinal Cone Photoreceptor Cells; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: C518238:CNGA3 protein, human; D054815:Cyclic Nucleotide-Gated Cation Channels; D004247:DNA
keywords: Achromatopsia; CNGA3 gene; Electroretinogram; Fundus autofluorescence; Optical coherence tomography