Hayashi Takaaki, Hosono Katsuhiro, Kurata Kentaro, Katagiri Satoshi, Mizobuchi Kei, Ueno Shinji, Kondo Mineo, Nakano Tadashi, Hotta Yoshihiro
Department of Ophthalmology, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
Department of Ophthalmology, Katsushika Medical Center, The Jikei University School of Medicine, 6-41-2 Aoto, Katsushika-ku, Tokyo, 125-8506, Japan.
Doc Ophthalmol. 2020 Apr;140(2):147-157. doi: 10.1007/s10633-019-09727-1. Epub 2019 Oct 3.
A single variant (p.G38D) in the GNAT1 gene, encoding the rod-specific transducin α-subunit in phototransduction, has been reported only in one French family with Nougaret-type autosomal dominant congenital stationary night blindness (CSNB). We identified a Japanese family with Nougaret-type CSNB and cone-rod dystrophy (CORD).
Five patients with CSNB and two patients with childhood-onset CORD were recruited. We performed a comprehensive ophthalmic examination including electroretinography (ERG). Disease-causing variants were identified by whole exome sequencing, with candidates confirmed by Sanger sequencing in nine family members.
The GNAT1 variant (p.G38D) was identified in all four CSNB patients, whereas the two CORD patients carried biallelic truncated known ABCA4 variants as well as the GNAT1 variant. Clinically, no remarkable findings were observed in fuduscopy, fundus autofluorescence, or optical coherence tomography images from the CSNB patients. No response was detectable by rod ERG. The a-waves of standard and bright flash ERG were delayed and broadened rather than biphasic, and b/a-wave amplitude ratio was negative. Cone and 30-Hz flicker responses were normal, and overall, the ERG findings were compatible with previous descriptions of Nougaret-type CSNB. ERG of the CORD patients with macular atrophy showed non-recordable rod response and severely decreased standard flash, cone and 30-Hz flicker responses.
This is the second report of a Nougaret-type CSNB family with the GNAT1 variant. Our novel findings suggest that coexistence of the GNAT1 and biallelic ABCA4 variants is associated with an overlapping phenotype with both Nougaret-type CSNB and CORD.
编码光转导中视杆特异性转导素α亚基的GNAT1基因中的单个变体（p.G38D），仅在一个患有努加雷型常染色体显性先天性静止性夜盲（CSNB）的法国家庭中被报道过。我们鉴定出一个患有努加雷型CSNB和锥杆营养不良（CORD）的日裔家庭。
招募了5名患有CSNB的患者和2名儿童期起病的CORD患者。我们进行了包括视网膜电图（ERG）在内的全面眼科检查。通过全外显子组测序鉴定致病变体，并在9名家庭成员中通过桑格测序确认候选变体。
在所有4名CSNB患者中均鉴定出GNAT1变体（p.G38D），而2名CORD患者携带双等位基因截短的已知ABCA4变体以及GNAT1变体。临床上，在CSNB患者的眼底镜检查、眼底自发荧光或光学相干断层扫描图像中未观察到明显异常。视杆ERG检测不到反应。标准闪光和强光闪光ERG的a波延迟且变宽，而非双相，b/a波幅比为负值。视锥和30Hz闪烁反应正常，总体而言，ERG结果与先前对努加雷型CSNB的描述相符。患有黄斑萎缩的CORD患者的ERG显示视杆反应不可记录，标准闪光、视锥和30Hz闪烁反应严重降低。
这是关于带有GNAT1变体的努加雷型CSNB家庭的第二篇报道。我们的新发现表明，GNAT1和双等位基因ABCA4变体的共存与努加雷型CSNB和CORD的重叠表型相关。
