Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001, Bern, Switzerland.
DermFocus, University of Bern, 3001, Bern, Switzerland.
Anim Genet. 2019 Dec;50(6):768-771. doi: 10.1111/age.12862. Epub 2019 Oct 1.
Congenital hemidysplasia with ichthyosiform nevus and limb defects syndrome in humans is a genodermatosis characterized by inflammatory linear verrucous epidermal nevi (ILVEN), often showing a striking lateralization pattern. It is caused by variants in the NSDHL gene encoding a 3β-hydroxysteroid dehydrogenase involved in the cholesterol biosynthesis pathway. In the present study, we investigated a female Chihuahua, which showed clinical and histological signs of ILVEN. We performed a candidate gene analysis in the affected animal. This analysis revealed a single missense variant in the NSDHL gene in the affected dog (XM_014111859.2:c.700G>A). The variant is predicted to cause a non-conservative amino acid change from glycine to arginine, XP_013967334.1:p.(Gly234Arg). The mutant allele was absent from WGS data of 594 genetically diverse dogs and eight wolves. Sanger sequencing confirmed that the variant was heterozygous in the affected dog and absent from 22 control Chihuahuas. Based on the knowledge about the functional impact of NSDHL variants in dogs and other species, c.700G>A is probably pathogenic and a convincing candidate causative variant for the observed skin lesions in the affected Chihuahua.
先天性半身发育不良伴鱼鳞痣和肢体缺陷综合征是一种皮肤遗传病，其特征为炎症性线状疣状表皮痣（ILVEN），常表现出明显的偏侧化模式。它是由编码胆固醇生物合成途径中 3β-羟甾脱氢酶的 NSDHL 基因突变引起的。在本研究中，我们对一只表现出 ILVEN 临床和组织学特征的雌性吉娃娃犬进行了研究。我们对患病动物进行了候选基因分析。该分析在受影响的犬中发现了 NSDHL 基因中的单个错义变异（XM_014111859.2:c.700G>A）。该变体预计会导致从甘氨酸到精氨酸的非保守氨基酸变化，XP_013967334.1:p.(Gly234Arg)。突变等位基因不存在于 594 只遗传多样化的犬和 8 只狼的 WGS 数据中。Sanger 测序证实，该变体在受影响的犬中为杂合子，在 22 只对照吉娃娃犬中不存在。基于 NSDHL 变异在犬和其他物种中的功能影响知识，c.700G>A 可能是致病性的，并且是导致受影响的吉娃娃犬观察到的皮肤病变的一个有说服力的候选致病变异。
