College of Medical, Veterinary & Life Sciences, University of Glasgow, 464 Bearsden Rd, Glasgow, G61 1QH, UK.
Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra 50Ozzano dell'Emilia, 40064, Bologna, Italy.
Acta Vet Scand. 2022 Sep 6;64(1):23. doi: 10.1186/s13028-022-00641-2.
Hypohidrotic ectodermal dysplasia (HED) is a congenital syndrome of mammals affecting organs and tissues of ectodermal origin characterized by absence or hypoplasia of hair, teeth, and eccrine glands. The disorder has been reported in several species, including humans, mice, dogs and cattle, associated with variants in genes affecting the ectodysplasin pathway, including the X-linked ectodysplasin A (EDA) gene. Until now, nine pathogenic variants have been found in the bovine EDA gene. Here we report a novel variant in EDA in a crossbreed male Belgian Blue calf with HED, and provide an overview of the phenotypic and allelic heterogeneity of EDA-related forms of HED in cattle.
A 45-day-old male crossbreed British Blue calf was referred with congenital hypotrichosis, oligodontia and omphalitis. On histopathological examination of the nasal planum, nasolabial glands and ducts were not observed. The density of hair follicles was low, and they were small, with a predominance of telogen-phase hairs, and some serocellular crusts. The phenotype of the calf resembled that of HED. Whole-genome sequencing (WGS) was performed and revealed a 21,899 base-pair deletion encompassing the coding exon 2 of EDA, predicted to result in an altered transcript and aberrant protein.
The clinicopathological and genetic findings were consistent with a case of X-linked HED. A very similar EDA deletion has been previously reported in a family of Holstein cattle with HED. The newly identified hemizygous EDA loss-of-function variant is certainly pathogenic and therefore is the genetic cause for the observed phenotype. This case report provides an additional example of the potential of WGS-based precise diagnostics in livestock species such as cattle to increase the diagnostic yield in rare diseases.
少汗型外胚层发育不良（HED）是一种影响外胚层起源的器官和组织的哺乳动物先天性综合征，其特征为毛发、牙齿和小汗腺缺失或发育不良。该疾病已在包括人类、小鼠、狗和牛在内的多个物种中报道，与影响外胚层蛋白途径的基因变异有关，包括 X 连锁的外胚层蛋白 A（EDA）基因。迄今为止，在牛 EDA 基因中已发现九个致病变异。在此，我们报道了一例具有 HED 的杂种雄性比利时蓝牛 EDA 基因的新型变异，并概述了牛中 EDA 相关形式的 HED 的表型和等位基因异质性。
一只 45 天大的雄性杂种英国蓝牛犊因先天性少毛症、少牙症和脐炎被转诊。鼻平面、鼻唇腺和导管的组织病理学检查未观察到。毛囊密度低，且较小，以休止期毛发为主，伴有一些浆液细胞鳞屑。牛犊的表型类似于 HED。进行全基因组测序（WGS），发现一个 21,899 碱基对的缺失，包含 EDA 的编码外显子 2，预计会导致转录物改变和异常蛋白。
临床病理和遗传学发现与 X 连锁 HED 一致。在一例具有 HED 的荷斯坦牛家族中，以前曾报道过非常相似的 EDA 缺失。新鉴定的 EDA 功能丧失杂合缺失变异肯定是致病的，因此是观察到的表型的遗传原因。该病例报告提供了一个额外的例子，说明基于 WGS 的精确诊断在牛等家畜物种中的潜力，可提高罕见疾病的诊断率。
