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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Published in:	Molecular vision Vol. 16; pp. 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:	Journal Article
Language:	English
Published:	United States Molecular Vision 12-03-2010
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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	1090-0535 1090-0535