TRPM1 mutations are associated with the complete form of congenital stationary night blindness

To identify human transient receptor potential cation channel, subfamily M, member 1 (TRPM1) gene mutations in patients with congenital stationary night blindness (CSNB). We analyzed four different Japanese patients with complete CSNB in whom previous molecular examination revealed no mutation in ei...

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Bibliographic Details
Published in:Molecular vision 2010-03, Vol.16, p.425-437
Main Authors: Nakamura, Makoto, Sanuki, Rikako, Yasuma, Tetsuhiro R, Onishi, Akishi, Nishiguchi, Koji M, Koike, Chieko, Kadowaki, Mikiko, Kondo, Mineo, Miyake, Yozo, Furukawa, Takahisa
Format: Article
Language:English
Subjects:
Adult
Animals
Base Sequence
Cell Line
Child
DNA Mutational Analysis
Electroretinography
Female
Genetic Predisposition to Disease
Heterozygote
Humans
Intracellular Space - metabolism
Male
Mice
Mice, Knockout
Molecular Sequence Data
Mutation - genetics
Mutation, Missense - genetics
Night Blindness - congenital
Night Blindness - genetics
Pedigree
Protein Transport
TRPM Cation Channels - deficiency
TRPM Cation Channels - genetics
TRPM Cation Channels - metabolism
Young Adult
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Summary:To identify human transient receptor potential cation channel, subfamily M, member 1 (TRPM1) gene mutations in patients with congenital stationary night blindness (CSNB). We analyzed four different Japanese patients with complete CSNB in whom previous molecular examination revealed no mutation in either nyctalopin (NYX) or glutamate receptor, metabotropic 6 (GRM6). The ophthalmologic examination included best-corrected visual acuity, refraction, biomicroscopy, ophthalmoscopy, fundus photography, Goldmann kinetic perimetry, color vision tests, and electroretinography (ERG). Exons 2 through 27 and the exon-intron junction regions of human TRPM1 were sequenced. Five different mutations in human TRPM1 were identified. Mutations were present in three unrelated patients with complete CSNB. All three patients were compound heterozygotes. Fundus examination revealed no abnormalities other than myopic changes, and the single bright-flash, mixed rod-cone ERG showed a "negative-type" configuration with a reduced normal a-wave and a significantly reduced b-wave amplitude. Our biochemical and cell biologic analyses suggest that the two identified IVS mutations lead to abnormal TRPM1 protein production, and imply that the two identified missense mutations lead to the mislocalization of the TRPM1 protein in bipolar cells (BCs). Human TRPM1 mutations are associated with the complete form of CSNB in Japanese patients, suggesting that TRPM1 plays an essential role in mediating the photoresponse in ON BCs in humans as well as in mice.
ISSN:1090-0535
1090-0535