BACKGROUND

Dermal mosaicism can result in skin disorders with specific distribution patterns of the lesions. The most common example is X-chromosomal functional mosaicism, in which the distribution pattern results from random X-chromosome inactivation (Lyonization) (Vreeburg & van Steensel, 2012). Three different skin patterns have been described, namely Blaschko lines, the checkerboard pattern and lateralization (Happle, 2006). Verrucous epidermal keratinocytic nevi (OMIA 002117) caused by variants in the X-chromosomal NSDHL gene may present with any of these patterns. The encoded NAD(P)H steroid dehydrogenase-like protein is a C4 demethylase involved in post-squalene cholesterol biosynthesis. Pathogenic NSDHL variants result in disruption of an essential step in cholesterol biosynthesis with a subsequent aggregation of toxic intermediates and a lack of cholesterol in the skin (Caldas & Herman, 2003; König et al., 2000). In heterozygous female dogs, this presents as a cornification disorder and is inherited as an X-linked semidominant trait (Bauer et al., 2017; Christen et al., 2020; Leuthard et al., 2019). NSDHL-associated disorders in humans cause a more severe phenotype involving congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD syndrome; König et al., 2000). In hemizygous males, such variants have been described as embryonic lethal (Happle et al., 1980).

中文翻译：

---

患有疣状表皮角化细胞痣的阿彭策尔山犬 NSDHL 基因杂合缺失

背景

真皮镶嵌可导致具有特定病变分布模式的皮肤疾病。最常见的例子是 X 染色体功能嵌合，其中分布模式是由随机 X 染色体失活（Lyonization）引起的（Vreeburg & van Steensel，  2012）。已经描述了三种不同的皮肤图案，即 Blaschko 线、棋盘图案和偏侧化（Happle，  2006）。由 X 染色体NSDHL基因变异引起的疣状表皮角化细胞痣 (OMIA 002117)可能会出现上述任何模式。编码的 NAD(P)H 类固醇脱氢酶样蛋白是参与角鲨烯后胆固醇生物合成的 C4 脱甲基酶。致病性NSDHL变异导致胆固醇生物合成的一个重要步骤被破坏，随后有毒中间体聚集并导致皮肤中胆固醇缺乏（Caldas & Herman，  2003；König 等，  2000）。在杂合雌性犬中，这表现为角化障碍，并作为 X 连锁半显性性状遗传（Bauer 等，  2017；Christen 等，  2020；Leuthard 等，  2019）。人类中的NSDHL相关疾病导致更严重的表型，涉及先天性偏侧发育不良、鱼鳞状痣和肢体缺陷（CHILD 综合征；König 等，  2000）。在半合子雄性中，此类变异被描述为胚胎致死性（Happle 等人，  1980）。