Novel mutations in the gene for α-subunit of retinal cone cyclic nucleotide-gated channels in a Japanese patient with congenital achromatopsia
| Autor: | Hisakazu Ogita, Kazushige Tsunoda, Futoshi Toyoda, Masahito Ohji, Akira Nakao, Kazuki Kuniyoshi, Hiroyuki Sakuramoto, Takeshi Iwata, Shuji Yamamoto, Yoshikazu Shimomura, Sanae Muraki-Oda, Hisao Ueyama, Motohiro Irifune |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Candidate gene medicine.medical_specialty Achromatopsia Genotype genetic structures DNA Mutational Analysis Cyclic Nucleotide-Gated Cation Channels Color Vision Defects Biology medicine.disease_cause Young Adult 03 medical and health sciences 0302 clinical medicine Ophthalmology Electroretinography medicine Humans Missense mutation GNAT2 Mutation medicine.diagnostic_test DNA General Medicine medicine.disease eye diseases Pedigree Phenotype 030104 developmental biology Retinal Cone Photoreceptor Cells 030221 ophthalmology & optometry Optometry Female Erg Tomography Optical Coherence |
| Zdroj: | Japanese Journal of Ophthalmology. 60:187-197 |
| ISSN: | 1613-2246 0021-5155 |
| DOI: | 10.1007/s10384-016-0424-6 |
| Popis: | To present the characteristics and pathology of a patient with congenital achromatopsia. 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. 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. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink