Department of Veterinary Medicine, Federal University of Paraná, Curitiba, Puerto Rico, Brazil.
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Vet Ophthalmol. 2023 Nov;26(6):532-547. doi: 10.1111/vop.13079. Epub 2023 Mar 5.
To describe the clinical, preliminary electroretinographic and optical coherence tomography features of a newly identified form of progressive retinal atrophy (PRA) in German Spitzes, and identify the causal gene mutation.
Thirty-three client-owned German Spitz dogs were included.
All animals underwent a full ophthalmic examination, including vision testing. In addition, fundus photography, ERG, and OCT were performed. A DNA-marker-based association analysis was performed to screen potential candidate genes and the whole genomes of four animals were sequenced.
Initial fundus changes were pale papilla and mild vascular attenuation. Oscillatory nystagmus was noted in 14 of 16 clinically affected puppies. Vision was impaired under both scotopic and photopic conditions. Rod-mediated ERGs were unrecordable in all affected dogs tested, reduced cone-mediated responses were present in one animal at 3 months of age and unrecordable in the other affected animals tested. Multiple small retinal bullae were observed in three clinically affected animals (two with confirmed genetic diagnosis). OCT showed that despite loss of function, retinal structure was initially well-preserved, although a slight retinal thinning developed in older animals with the ventral retina being more severely affected. Pedigree analysis supported an autosomal recessive inheritance. A mutation was identified in GUCY2D, which segregated with the disease (NM_001003207.1:c.1598_1599insT; p.(Ser534GlufsTer20)). Human subjects with GUCY2D mutations typically show an initial disconnect between loss of function and loss of structure, a feature recapitulated in the affected dogs in this study.
We identified early-onset PRA in the German Spitz associated with a frameshift mutation in GUCY2D.
描述德国牧羊犬中一种新发现的进行性视网膜萎缩（PRA）的临床、初步视网膜电图和光学相干断层扫描特征，并确定致病基因突变。
共纳入 33 只客户所有的德国牧羊犬。
所有动物均接受全面眼科检查，包括视力测试。此外，还进行了眼底照相、ERG 和 OCT 检查。进行了基于 DNA 标记的关联分析，以筛选潜在的候选基因，并对 4 只动物的全基因组进行测序。
最初的眼底变化为苍白视盘和轻度血管衰减。16 只临床受影响的幼犬中有 14 只出现眼球震颤。在暗适应和明适应条件下视力均受损。所有受检受影响的犬均无法记录到杆状细胞介导的 ERG，1 只动物在 3 月龄时出现降低的锥状细胞介导的反应，其余受检受影响的动物则无法记录到。3 只临床受影响的动物（2 只具有确诊遗传诊断）观察到多个小视网膜泡。OCT 显示，尽管功能丧失，但视网膜结构最初仍保持良好，尽管在年龄较大的动物中出现轻微的视网膜变薄，且腹侧视网膜受影响更严重。家系分析支持常染色体隐性遗传。在 GUCY2D 中发现了一个突变，该突变与疾病分离（NM_001003207.1：c.1598_1599insT；p.（Ser534GlufsTer20））。具有 GUCY2D 突变的人类患者通常表现出功能丧失与结构丧失之间的初始分离，这一特征在本研究中受影响的犬中得到了重现。
我们在德国牧羊犬中发现了一种与 GUCY2D 框移突变相关的早发性 PRA。
