Mutations in GRM6 cause autosomal recessive congenital stationary night blindness with a distinctive scotopic 15-Hz flicker electroretinogram.
Mutations in GRM6 cause autosomal recessive congenital stationary night blindness with a distinctive scotopic 15-Hz flicker electroretinogram.
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DOI：
10.1167/iovs.05-0526
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发表时间：
2005-11
影响因子：
4.4
通讯作者：
C. Zeitz;M. V. van Genderen;J. Neidhardt;U. Luhmann;F. Hoeben;U. Forster;K. Wycisk;G. Mátyás;C. Hoyng;F. Riemslag;F. Meire;F. Cremers;W. Berger
中科院分区：
文献类型：
--
作者：
C. Zeitz;M. V. van Genderen;J. Neidhardt;U. Luhmann;F. Hoeben;U. Forster;K. Wycisk;G. Mátyás;C. Hoyng;F. Riemslag;F. Meire;F. Cremers;W. Berger
先天性静止性夜盲（Congenital stationary night blindness，CSNB）是一组以常染色体显性遗传、常染色体隐性遗传或X-连锁遗传的夜间视力受损为特征的非进行性视网膜疾病。常染色体隐性（ar）CSNB似乎非常罕见。缺乏代谢型谷氨酸受体6（Grm 6）的小鼠在从光感受器到ON双极细胞的信号传递中存在缺陷。在目前的研究中，人类直系同源物（GRM 6）被筛选为arCSNB的可能候选者。方法对5个arCSNB家系进行GRM 6基因突变筛查。随后，用标准和15-Hz闪烁视网膜电图（ERG）检查。将这些记录与X连锁CSNB 1患者的记录进行比较。结果5个家系中有3个家系的患者携带GRM 6复合杂合或纯合突变。引人注目的是，他们都表现出一个独特的异常杆通路信号暗视15赫兹闪烁ERG。结论：本研究中发现的新特征表明存在两个以上的视杆细胞通路。在X连锁CSNB 1患者和其他分子缺陷未知的受影响个体中未观察到独特的ERG特征。这些观察结果将有助于通过ERG和分子遗传学分析来区分常染色体隐性遗传和X连锁隐性遗传病例。
PURPOSE Congenital stationary night blindness (CSNB) is a group of nonprogressive retinal disorders characterized by impaired night vision that occurs in autosomal dominant, autosomal recessive, or X-linked forms. Autosomal recessive (ar)CSNB seems to be very rare. Mice lacking the metabotropic glutamate receptor 6 (Grm6) have a defect in signal transmission from the photoreceptors to ON-bipolar cells. In the current study, the human orthologue (GRM6) was screened as a likely candidate for arCSNB. METHODS arCSNB individuals of five families were screened for mutations in GRM6. Subsequently, they were examined with standard and 15-Hz flicker electroretinography (ERG). These recordings were compared with those of patients with X-linked CSNB1. RESULTS Affected individuals in three of five families carried either compound heterozygous or homozygous mutations in GRM6. Strikingly, all of them displayed a distinctive abnormality of the rod pathway signals on scotopic 15-Hz flicker ERG. CONCLUSIONS The novel profile identified in this study suggests the existence of more than two rod pathways. The distinctive ERG feature was not observed in patients with X-linked CSNB1 and additional affected individuals with unknown molecular defect. These observations will help to discriminate autosomal recessive from X-linked recessive cases by ERG and molecular genetic analysis.