A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration

作者：Carrigan Matthew^*; Duignan Emma; Humphries Pete; Palfi Arpad; Kenna Paul F; Farrar G Jane

来源：British Journal of Ophthalmology, 2016, 100(4): 495-500.

DOI：10.1136/bjophthalmol-2015-306939

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.

• 出版日期2016-4