Institute of Medical Genetics, Cardiff University, Cardiff, United Kingdom ; Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
PLoS One. 2013 Dec 4;8(12):e81625. doi: 10.1371/journal.pone.0081625. eCollection 2013.
Ectodermal dysplasias (EDs) are a large and heterogeneous group of hereditary disorders characterized by abnormalities in structures of ectodermal origin. Incontinentia pigmenti (IP) is an ED characterized by skin lesions evolving over time, as well as dental, nail, and ocular abnormalities. Due to X-linked dominant inheritance IP symptoms can only be seen in female individuals while affected males die during development in utero. We observed a family of horses, in which several mares developed signs of a skin disorder reminiscent of human IP. Cutaneous manifestations in affected horses included the development of pruritic, exudative lesions soon after birth. These developed into wart-like lesions and areas of alopecia with occasional wooly hair re-growth. Affected horses also had streaks of darker and lighter coat coloration from birth. The observation that only females were affected together with a high number of spontaneous abortions suggested an X-linked dominant mechanism of transmission. Using next generation sequencing we sequenced the whole genome of one affected mare. We analyzed the sequence data for non-synonymous variants in candidate genes and found a heterozygous nonsense variant in the X-chromosomal IKBKG gene (c.184C>T; p.Arg62*). Mutations in IKBKG were previously reported to cause IP in humans and the homologous p.Arg62* variant has already been observed in a human IP patient. The comparative data thus strongly suggest that this is also the causative variant for the observed IP in horses. To our knowledge this is the first large animal model for IP.
表皮发育不全症（EDs）是一组由外胚层起源的结构异常引起的遗传性疾病，其种类繁多且具有异质性。色素失禁症（IP）是一种 ED，其特征是皮肤病变随时间推移而演变，还伴有牙齿、指甲和眼部异常。由于 X 连锁显性遗传，只有女性个体才能出现 IP 症状，而受影响的男性在子宫内发育过程中死亡。我们观察到一个马群，其中几匹母马出现了类似于人类 IP 的皮肤疾病迹象。受影响马匹的皮肤表现包括在出生后不久出现瘙痒、渗出性病变。这些病变发展成疣状病变和脱发区域，偶尔会有羊毛状毛发再生。受影响的马匹从出生起就有条纹状的颜色变深和变浅的毛色。仅女性受影响且自发性流产数量较多的观察结果表明，这是一种 X 连锁显性遗传机制。我们使用下一代测序技术对一匹受影响的母马进行了全基因组测序。我们分析了候选基因中的非同义变异序列数据，发现 X 染色体 IKBKG 基因（c.184C>T;p.Arg62*）存在杂合性无义变异。IKBKG 突变先前被报道可导致人类出现 IP，而同源性 p.Arg62* 变异已在人类 IP 患者中观察到。因此，比较数据强烈表明这也是导致所观察到的马的 IP 的致病变异。据我们所知，这是第一个 IP 的大型动物模型。
