Mutations in TRPM1 Are a Common Cause of Complete Congenital Stationary Night Blindness
Mutations in TRPM1 Are a Common Cause of Complete Congenital Stationary Night Blindness
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DOI：
10.1016/j.ajhg.2009.10.012
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发表时间：
2009-11-13
影响因子：
9.8
通讯作者：
Kamermans, Maarten
中科院分区：
文献类型：
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作者：
van Genderen, Maria M.;Bijveld, Mieke M. C.;Kamermans, Maarten
先天性静止性夜盲症（CSNB）是一组临床和遗传上异质性的视网膜疾病，其特征是非进行性夜视力受损和不同程度的视力下降。我们在此报告，患有常染色体隐性完全性 CSNB (cCSNB) 的 8 名女性先证者中，有 6 名存在 TRPM1 突变，TRPM1 是一种视网膜瞬时受体电位 (TRP) 阳离子通道基因。这些数据表明 TRMP1 突变是欧洲血统个体常染色体隐性 CSNB 的主要原因。我们将人类视网膜中的 TRPM I 定位于外丛层中的 ON 双极细胞树突。我们的结果表明，在人类中，TRPM1 是由 mGluR6 (GRM6) 信号级联门控的通道，导致 ON 双极细胞的光诱发反应。最后，我们表明，详细的视网膜电图检查是区分 TRPM1 或 GRM6（另一种常染色体隐性 cCSNB 疾病基因）突变患者的有效方法。这些结果增加了不同组的 TRP 通道在人类疾病中日益增长的重要性，也为视网膜回路提供了新的见解。
Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous group of retinal disorders characterized by nonprogressive impaired night vision and variable decreased visual acuity. We report here that six out of eight female probands with autosomal-recessive complete CSNB (cCSNB) had mutations in TRPM1, a retinal transient receptor potential (TRP) cation channel gene. These data suggest that TRMP1 mutations are a major cause of autosomal-recessive CSNB in individuals of European ancestry. We localized TRPM I in human retina to the ON bipolar cell dendrites in the outer plexifom layer. Our results suggest that in humans, TRPM1 is the channel gated by the mGluR6 (GRM6) signaling cascade, which results in the light-evoked response of ON bipolar cells. Finally, we showed that detailed electroretinography is an effective way to discriminate among patients with mutations in either TRPM1 or GRM6, another autosomal-recessive cCSNB disease gene. These results add to the growing importance of the diverse group of TRP channels in human disease and also provide new insights into retinal circuitry.