Novel mutations in the gene for α-subunit of retinal cone cyclic nucleotide-gated channels in a Japanese patient with congenital achromatopsia

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, perimet...

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Bibliographic Details
Published in:Japanese journal of ophthalmology 2016-05, Vol.60 (3), p.187-197
Main Authors: Kuniyoshi, Kazuki, Muraki-Oda, Sanae, Ueyama, Hisao, Toyoda, Futoshi, Sakuramoto, Hiroyuki, Ogita, Hisakazu, Irifune, Motohiro, Yamamoto, Shuji, Nakao, Akira, Tsunoda, Kazushige, Iwata, Takeshi, Ohji, Masahito, Shimomura, Yoshikazu
Format: Article
Language:English
Subjects:
Clinical Investigation
Color Vision Defects - diagnosis
Color Vision Defects - genetics
Color Vision Defects - metabolism
Cyclic Nucleotide-Gated Cation Channels - genetics
Cyclic Nucleotide-Gated Cation Channels - metabolism
DNA - genetics
DNA Mutational Analysis
Electroretinography
Female
Genotype
Humans
Medicine
Medicine & Public Health
Mutation
Ophthalmology
Pedigree
Phenotype
Retinal Cone Photoreceptor Cells
Tomography, Optical Coherence
Young Adult
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Summary: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.
ISSN:0021-5155
1613-2246
DOI:10.1007/s10384-016-0424-6