Horae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
Department of Radiology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
J Vet Intern Med. 2023 Sep-Oct;37(5):1716-1724. doi: 10.1111/jvim.16805. Epub 2023 Aug 18.
Ehlers-Danlos syndromes (EDS) are a heterogeneous group of heritable connective tissue disorders occurring in both human and veterinary patients. The genetics of these disorders are poorly described in small animal patients.
HYPOTHESIS/OBJECTIVES: Define the clinical manifestations and genetic cause of a suspected form of EDS in a cat.
A 14-week-old male domestic medium hair cat was presented with skin hyperextensibility and fragility. The classic tragic facial expression was observed as well as chronic pruritus and mild hyperesthesia.
Blood samples and a skin biopsy sample were collected from the affected cat. Clinical examinations, histology, electron microscopy and whole genome sequencing were conducted to characterize the clinical presentation and identify possible pathogenic DNA variants to support a diagnosis. Criteria defining variant pathogenicity were examined including human disease variant databases.
Histology showed sparse, disorganized collagen and an increase in cutaneous mast cells. Electron microscopy identified ultrastructural defects commonly seen in collagen type V alpha 1 chain (COL5A1) variants including flower-like collagen fibrils in cross-section. Whole genome sequencing and comparison with 413 cats in the 99 Lives Cat Genome Sequencing Consortium database identified a novel splice acceptor site variant at exon 4 in COL5A1 (c.501-2A>C).
Our report broadens the current understanding of EDS in veterinary patients and supports the use of precision medicine techniques in clinical veterinary practice. The classification of variants for pathogenicity should be considered in companion animals.
埃勒斯-当洛斯综合征（EDS）是一组遗传性结缔组织疾病，发生在人和兽医患者中。这些疾病在小动物患者中的遗传学描述很差。
假设/目的：定义一只猫疑似 EDS 形式的临床表现和遗传原因。
一只 14 周大的雄性国内中等毛猫表现出皮肤过度伸展和脆弱。观察到典型的悲惨面部表情以及慢性瘙痒和轻度感觉过敏。
从受影响的猫中采集血液样本和皮肤活检样本。进行临床检查、组织学、电子显微镜检查和全基因组测序，以描述临床表现并确定可能的致病 DNA 变异体，以支持诊断。检查了定义变异致病性的标准，包括人类疾病变异数据库。
组织学显示稀疏、组织紊乱的胶原和皮肤肥大细胞增加。电子显微镜鉴定出 COL5A1 中常见的超微结构缺陷，包括横截面呈花状的胶原纤维。全基因组测序并与 99 只生命猫基因组测序联盟数据库中的 413 只猫进行比较，发现 COL5A1 外显子 4 中的一个新剪接受体位点变异（c.501-2A>C）。
我们的报告拓宽了兽医患者中 EDS 的现有认识，并支持在临床兽医实践中使用精准医学技术。应考虑伴侣动物中变异体的致病性分类。
