Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland.
Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Genes (Basel). 2021 Sep 23;12(10):1479. doi: 10.3390/genes12101479.
A 1-month-old, female, smooth-haired miniature Dachshund with dilute color and neurological defects was investigated. The aim of this study was to characterize the clinical signs, histopathological changes and underlying genetic defect. The puppy had visible coat color dilution and was unable to hold its head on its own or to remain in a stable prone position for an extended period. Histopathological examination revealed an accumulation of clumped melanin and deposition of accumulated keratin within the hair follicles, accompanied by dermal pigmentary incontinence. These dermatological changes were compatible with the histopathology described in dogs with an -related dilute coat color. We sequenced the genome of the affected dog and compared the data to 795 control genomes. , coding for myosin VA, was investigated as the top functional candidate gene. This search revealed a private homozygous frameshift variant in , XM_022412522.1:c.4973_4974insA, predicted to truncate 269 amino acids (13.8%) of the wild type myosin VA protein, XP_022268230.1:p.(Asn1658Lysfs*28). The genotypes of the index family showed the expected co-segregation with the phenotype and the mutant allele was absent from 142 additionally genotyped, unrelated Dachshund dogs. loss of function variants cause Griscelli type 1 syndrome in humans, lavender foal in horses and the phenotype of the mouse mutant. Based on the available data, together with current knowledge on other species, we propose the identified frameshift insertion as a candidate causative variant for the observed dermatological and neurological signs in the investigated dog.
一只 1 月龄、雌性、短毛小型腊肠犬，毛色浅淡，存在神经缺陷，对此进行了研究。本研究旨在描述临床症状、组织病理学变化和潜在的遗传缺陷。该幼犬可见毛色稀释，无法自行抬头或长时间保持稳定的俯趴姿势。组织病理学检查显示黑色素聚集和角蛋白在毛囊内堆积，并伴有皮肤色素失禁。这些皮肤变化与描述的毛色稀释的犬的组织病理学变化一致。我们对受影响犬的基因组进行了测序，并将数据与 795 个对照基因组进行了比较。作为功能候选基因，我们研究了编码肌球蛋白 VA 的 。该搜索发现了一个在 中特有的纯合移码变异，XM_022412522.1:c.4973_4974insA，预测截短了野生型肌球蛋白 VA 蛋白的 269 个氨基酸（13.8%），XP_022268230.1:p.(Asn1658Lysfs*28)。索引家族的基因型显示与表型的预期共分离，且突变等位基因不存在于 142 个额外的、无关的腊肠犬中。 在人类中引起 Griscelli 综合征 1 型，在马中引起薰衣草驹，在 突变鼠中引起表型。基于现有数据，并结合其他物种的现有知识，我们提出鉴定的 移码插入是观察到的犬皮肤和神经症状的候选致病变异。
