AniCura Tierärztliche Spezialisten, 22043 Hamburg, Germany.
Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland.
Genes (Basel). 2020 Apr 28;11(5):481. doi: 10.3390/genes11050481.
A 4-month-old female Irish Terrier presented with a well demarcated ulcerative and crusting lesion in the right ear canal. Histological analysis revealed epidermal hyperplasia with severe acantholysis affecting all suprabasal layers of the epidermis, which prompted a presumptive diagnosis of canine Darier disease. The lesion was successfully treated by repeated laser ablation of the affected epidermis. Over the course of three years, the dog additionally developed three dermal nodules of up to 4 cm in diameter that were excised and healed without complications. Histology of the excised tissue revealed multiple infundibular cysts extending from the upper dermis to the subcutis. The cysts were lined by squamous epithelium, which presented with abundant acantholysis of suprabasal keratinocytes. Infundibular cysts represent a novel finding not previously reported in Darier patients. Whole genome sequencing of the affected dog was performed, and the functional candidate genes for Darier disease () and Hailey-Hailey disease () were investigated. The analysis revealed a heterozygous SINE insertion into the gene, at the end of intron 14, close to the boundary of exon 15. Analysis of the mRNA from skin of the affected dog demonstrated a splicing defect and marked allelic imbalance, suggesting nonsense-mediated decay of the resulting aberrant transcripts. As Darier disease in humans is caused by haploinsufficiency of , our genetic findings are in agreement with the clinical and histopathological data and support the diagnosis of canine Darier disease.
一只 4 月龄雌性爱尔兰梗表现出右耳道界限清楚的溃疡性和结痂性病变。组织学分析显示表皮过度增生，伴有严重棘层松解，影响表皮所有基底上层，这促使我们做出犬 Darier 病的初步诊断。通过反复激光消融受影响的表皮，成功治疗了病变。在接下来的三年中，这只狗还额外发展了三个直径达 4 厘米的皮肤结节，这些结节被切除并愈合，没有出现并发症。切除组织的组织学显示多个从真皮延伸到皮下组织的漏斗状囊肿。囊肿由鳞状上皮衬里，表现为大量棘层松解的基底上层角蛋白细胞。漏斗状囊肿是 Darier 病患者中以前未报道过的新发现。对受影响的狗进行了全基因组测序，并研究了 Darier 病（）和 Hailey-Hailey 病（）的功能候选基因。分析显示，一个 SINE 插入物位于 14 号内含子的末端，靠近 15 号外显子的边界，这是一个杂合子。对受影响狗皮肤的 mRNA 进行分析显示存在剪接缺陷和明显的等位基因失衡，这表明异常转录物的无意义介导衰变。由于人类的 Darier 病是由于 的单倍体不足引起的，因此我们的遗传发现与临床和组织病理学数据一致，并支持犬 Darier 病的诊断。
