Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6
Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6
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DOI：
10.1073/pnas.0501233102
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发表时间：
2005-03-29
影响因子：
11.1
通讯作者：
Rajagopalan, AS
中科院分区：
文献类型：
--
作者：
Dryja, TP;McGee, TL;Rajagopalan, AS
我们报告了三个不相关的患者突变的GRM 6基因，通常编码谷氨酸受体mGluR 6。这种神经递质受体先前已被证明仅存在于ON双极细胞树突的突触中，并且它介导从视杆和视锥光感受器到这种类型的二级神经元的突触传递。尽管存在突触缺陷，但最佳视力正常或仅中度降低（20/15至20/40）。这些患者从很小的时候就患有夜盲症，当他们最大程度地适应黑暗时，他们只能感知到强度等于或略暗于锥体系统正常检测到的强度的光（即，2-3 log单位高于正常值）。视网膜电图（ERG）对单次短暂闪光的反应具有清晰可检测的a波，其来自光感受器，以及大大降低的b波，其来自二级内部视网膜神经元。对闪烁光反应的ERG显示ON反应明显降低，OFF反应接近正常。在灰色背景上突然出现的白色与黑色物体的感知中没有主观延迟。这些患者是一种以前未被识别的常染色体隐性遗传形式的先天性夜盲症，与负ERG波形相关。
We report three unrelated patients with mutations in the GRM6 gene that normally encodes the glutamate receptor mGluR6. This neurotransmitter receptor has been shown previously to be present only in the synapses of the ON bipolar cell dendrites, and it mediates synaptic transmission from rod and cone photoreceptors to this type of second-order neuron. Despite the synaptic defect, best visual acuities were normal or only moderately reduced (20/15 to 20/40). The patients were night blind from an early age, and when maximally dark-adapted, they could perceive lights only with an intensity equal to or slightly dimmer than that normally detected by the cone system (i.e., 2-3 log units above normal). Electroretinograms (ERGs) in response to single brief flashes of light had clearly detectable a-waves, which are derived from photoreceptors, and greatly reduced b-waves, which are derived from the second-order inner retinal neurons. ERGs in response to sawtooth flickering light indicated a markedly reduced ON response and a nearly normal OFF response. There was no subjective delay in the perception of suddenly appearing white vs. black objects on a gray background. These patients exemplify a previously unrecognized, autosomal recessive form of congenital night blindness associated with a negative ERG waveform.