A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration
A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration
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DOI：
10.1136/bjophthalmol-2015-306939
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发表时间：
2016-04-01
影响因子：
4.1
通讯作者：
Farrar, G. Jane
中科院分区：
文献类型：
--
作者：
Carrigan, Matthew;Duignan, Emma;Farrar, G. Jane
GNAT 1基因编码视杆细胞转导蛋白a亚基，视杆细胞光转导级联反应的关键元件。GNAT 1的变体在过去与静止性夜盲症有关，但与同一途径中的其他蛋白质不同，方法对一组182个视网膜病变相关基因进行测序，结果测序结果显示，在1例遗传性视网膜病变患者中，GNAT 1基因存在一种新的纯合性截短突变，色素性障碍和视野收缩，表现与色素性视网膜炎一致。这是第一个报告的病人纯合子的功能完全丧失GNAT1突变。该患者的临床数据提供了明确的证据，视网膜色素变性与晚发除了终身夜盲，将预期从transducin functions.Conclusion缺乏这些数据表明，一些截短GNAT 1变异确实可以导致隐性的，轻度的，晚发性视网膜变性在人类，而不仅仅是静止夜盲症如以前报道的。与Gnat 1敲除小鼠的表型有显著的相似性。
Background The GNAT1 gene encodes the a subunit of the rod transducin protein, a key element in the rod phototransduction cascade. Variants in GNAT1 have been implicated in stationary night-blindness in the past, but unlike other proteins in the same pathway, it has not previously been implicated in retinitis pigmentosa.Methods A panel of 182 retinopathy-associated genes was sequenced to locate disease-causing mutations in patients with inherited retinopathies.Results Sequencing revealed a novel homozygous truncating mutation in the GNAT1 gene in a patient with significant pigmentary disturbance and constriction of visual fields, a presentation consistent with retinitis pigmentosa. This is the first report of a patient homozygous for a complete loss-of-function GNAT1 mutation. The clinical data from this patient provide definitive evidence of retinitis pigmentosa with late onset in addition to the lifelong night-blindness that would be expected from a lack of transducin function.Conclusion These data suggest that some truncating GNAT1 variants can indeed cause a recessive, mild, lateonset retinal degeneration in human beings rather than just stationary night-blindness as reported previously, with notable similarities to the phenotype of the Gnat1 knockout mouse.