A Nonsense Mutation in the IKBKG Gene in Mares with Incontinentia Pigmenti.

Towers, Rachel E; Murgiano, Leonardo; Millar, David S; Glen, Elise; Topf, Ana; Jagannathan, Vidhya; Drögemüller, Cord; Goodship, Judith A; Clarke, Angus J; Leeb, Tosso (2013). A Nonsense Mutation in the IKBKG Gene in Mares with Incontinentia Pigmenti. PLoS ONE, 8(12), e81625. Public Library of Science 10.1371/journal.pone.0081625

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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:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > DermFocus
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Murgiano, Leonardo; Jagannathan, Vidya; Drögemüller, Cord and Leeb, Tosso

Subjects:

500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Susanne Portner

Date Deposited:

24 Jul 2014 16:26

Last Modified:

16 Feb 2015 08:00

Publisher DOI:

10.1371/journal.pone.0081625

PubMed ID:

24324710

BORIS DOI:

10.7892/boris.43847

URI:

https://boris.unibe.ch/id/eprint/43847

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