Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

A nonsense mutation in the IKBKG gene in mares with incontinentia pigmenti

Mantovani, Roberto, Towers, Rachel E., Murgiano, Leonardo, Millar, David S., Glen, Elise, Topf, Ana, Jagannathan, Vidhya, Drögemüller, Cord, Goodship, Judith A., Clarke, Angus J. and Leeb, Tosso 2013. A nonsense mutation in the IKBKG gene in mares with incontinentia pigmenti. PLoS ONE 8 (12) , e81625. 10.1371/journal.pone.0081625

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (328kB) | Preview

Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Public Library of Science
ISSN: 1932-6203
Date of First Compliant Deposit: 6 March 2018
Date of Acceptance: 25 October 2013
Last Modified: 28 Apr 2019 12:05
URI: http://orca.cf.ac.uk/id/eprint/109699

Citation Data

Cited 10 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics