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Home / Equine Research Bank / PLoS One / A nonsense mutation in the IKBKG gene in mares with incontin...
PloS one2013; 8(12); e81625; doi: 10.1371/journal.pone.0081625

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

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.
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Publication Date: 2013-12-04 PubMed ID: 24324710PubMed Central: PMC3852476DOI: 10.1371/journal.pone.0081625Google Scholar: Lookup
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  • Non-U.S. Gov't

Summary

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The research article discusses a genetic mutation in horses that mirrors the symptoms of a skin disorder in humans known as Incontinentia Pigmenti (IP), which is a result of a mutation in the IKBKG gene. This discovery paves the way for the first large animal model for IP.

Understanding Incontinentia Pigmenti

  • Incontinentia Pigmenti (IP) is a condition categorized under the umbrella of ectodermal dysplasias, a group of hereditary disorders that cause abnormalities in the ectodermal structures, the outer tissues of the body including skin, hair, teeth, and sweat glands.
  • IP typically exhibits skin lesions that evolve over time, along with anomalies in dental, nail, and ocular structures.
  • This condition is passed down through an X-linked dominant inheritance pattern, which means it primarily affects females, as males with the disorder often do not survive in utero.

Observation and Findings in Horses

  • Experts observed a group of horses where several of the females showed signs of a skin disorder similar to human IP.
  • Symptoms included pruritic, exudative lesions appearing shortly after birth that evolved into wart-like lesions and areas of baldness. Some areas displayed irregular wooly hair re-growth.
  • There were also patches of varied coat coloration exhibited from birth, and a high number of spontaneous abortions, strengthening the hypothesis of X-linked dominant transmission.

Genetic Analysis and Intervention

  • Researchers conducted whole-genome sequencing using next-gen sequencing technology to investigate the DNA of one affected horse.
  • The sequence data were analyzed to identify non-synonymous variants in candidate genes – these are variants that alter protein sequence and potentially function.
  • A heterozygous nonsense variant in the X-chromosomal IKBKG gene, c.184C>T (p.Arg62*), was identified. Nonsense variants are a type of mutation where a stop codon is introduced prematurely, leading to truncated, often non-functional proteins.
  • Previously recorded mutations in the IKBKG gene have been associated with causing IP in humans. The exact p.Arg62* variant discovered in aforementioned horse has already been noted in a human patient with IP.
  • This comparative evidence strongly indicates that this variant is responsible for IP in horses, and this marks the first time a large animal model for IP has been identified.

Cite This Article

APA
Towers RE, Murgiano L, Millar DS, Glen E, Topf A, Jagannathan V, Drögemüller C, Goodship JA, Clarke AJ, Leeb T. (2013). A nonsense mutation in the IKBKG gene in mares with incontinentia pigmenti. PLoS One, 8(12), e81625. https://doi.org/10.1371/journal.pone.0081625

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 8
Issue: 12
Pages: e81625
PII: e81625

Researcher Affiliations

Towers, Rachel E
  • Institute of Medical Genetics, Cardiff University, Cardiff, United Kingdom ; Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
Murgiano, Leonardo
    Millar, David S
      Glen, Elise
        Topf, Ana
          Jagannathan, Vidhya
            Drögemüller, Cord
              Goodship, Judith A
                Clarke, Angus J
                  Leeb, Tosso

                    MeSH Terms

                    • Animals
                    • Base Sequence
                    • Codon, Nonsense / genetics
                    • Exons / genetics
                    • Female
                    • Genome / genetics
                    • Horses / genetics
                    • Humans
                    • I-kappa B Kinase / genetics
                    • Incontinentia Pigmenti / genetics
                    • Male
                    • Molecular Sequence Data
                    • Pedigree
                    • Phenotype
                    • RNA, Messenger / genetics
                    • RNA, Messenger / metabolism
                    • Sequence Analysis, DNA

                    Conflict of Interest Statement

                    The authors have declared that no competing interests exist.

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                    This article has been cited 7 times.
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