期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 92, 期 1, 页码 67-75出版社
CELL PRESS
DOI: 10.1016/j.ajhg.2012.10.023
关键词
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资金
- Retina France (100 Exome Project)
- Foundation Voir et Entendre
- Foundation Fighting Blindness (FFB) [CD-CL-0808-0466-CHNO, C-CMM-0907-0428-INSERM04]
- Ville de Paris and Region Ile de France
- French Association against Myopathy [KBM-14390]
- Institut National de la Sante et de la Recherche Medicale/Indian Council of Medical Research [53/1/Indo-Foreign/Oph/10-NCD-II]
Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous retinal disorder. Two forms can be distinguished clinically: complete CSNB (cCSNB) and incomplete CSNB. Individuals with cCSNB have visual impairment under low-light conditions and show a characteristic electroretinogram (ERG). The b-wave amplitude is severely reduced in the dark-adapted state of the ERG, representing abnormal function of ON bipolar cells. Furthermore, individuals with cCSNB can show other ocular features such as nystagmus, myopia, and strabismus and can have reduced visual acuity and abnormalities of the cone ERG waveform. The mode of inheritance of this form can be X-linked or autosomal recessive, and the dysfunction of four genes (NYX, GRM6, TRPM1, and GPR179) has been described so far. Whole-exome sequencing in one simplex cCSNB case lacking mutations in the known genes led to the identification of a missense mutation (c.983G>A [p.Cys328Tyr]) and a nonsense mutation (c.1318C>T [p.Arg440*]) in LRIT3, encoding leucine-rich-repeat (LRR), immunoglobulin-like, and transmembrane-domain 3 (LRIT3). Subsequent Sanger sequencing of 89 individuals with CSNB identified another cCSNB case harboring a nonsense mutation (c.1151C>G [p.Ser384*]) and a deletion predicted to lead to a premature stop codon (c.1538_1539del [p.Ser513Cysfs*59]) in the same gene. Human LRIT3 antibody staining revealed in the outer plexiform layer of the human retina a punctate-labeling pattern resembling the dendritic tips of bipolar cells; similar patterns have been observed for other proteins implicated in cCSNB. The exact role of this LRR protein in cCSNB remains to be elucidated.
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