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Lookup NU author(s): Dr Elise Glen, Dr Ana TopfORCiD, Professor Judith Goodship
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.
Author(s): Towers RE, Murgiano L, Millar DS, Glen E, Topf A, Jagannathan V, Drogemuller C, Goodship JA, Clarke AJ, Leeb T
Publication type: Article
Publication status: Published
Journal: PLoS ONE
Year: 2013
Volume: 8
Issue: 12
Online publication date: 04/12/2013
Acceptance date: 25/10/2013
Date deposited: 04/11/2014
ISSN (electronic): 1932-6203
Publisher: Public Library of Science
URL: http://dx.doi.org/10.1371/journal.pone.0081625
DOI: 10.1371/journal.pone.0081625
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