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A Frameshift Mutation within LAMC2 Is Responsible for Herlitz Type Junctional Epidermolysis Bullosa (HJEB) in Black Headed Mutton Sheep

By Stefanie Mömke, Andrea Kerkmann, Anne Wöhlke, Miriam Ostmeier, Marion Hewicker-Trautwein, Martin Ganter, James Kijas and Ottmar Distl


Junctional epidermolysis bullosa (JEB) is a hereditary mechanobullous skin disease in humans and animals. A Herlitz type JEB was identified in German Black Headed Mutton (BHM) sheep and affected lambs were reproduced in a breeding trial. Affected lambs showed skin and mucous membranes blistering and all affected lambs died within the first weeks of life. The pedigree data were consistent with a monogenic autosomal recessive inheritance. Immunofluorescence showed a reduced expression of laminin 5 protein which consists of 3 subunits encoded by the genes LAMA3, LAMB3 and LAMC2. We screened these genes for polymorphisms. Linkage and genome-wide association analyses identified LAMC2 as the most likely candidate for HJEB. A two base pair deletion within exon 18 of the LAMC2 gene (FM872310:c.2746delCA) causes a frameshift mutation resulting in a premature stop codon (p.A928*) 13 triplets downstream of this mutation and in addition, introduces an alternative splicing of exon 18 LAMC2. This deletion showed a perfect co-segregation with HJEB in all 740 analysed BHM sheep. Identification of the LAMC2 deletion means an animal model for HJEB is now available to develop therapeutic approaches of relevance to the human form of this disease

Topics: Research Article
Publisher: Public Library of Science
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Provided by: PubMed Central

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  1. (1988). A disease resembling junctional epidermolysis bullosa in a toy poodle.
  2. (2003). A mutation in the LAMC2 gene causes the Herlitz junctional epidermolysis bullosa (H-JEB) in two French draft horse breeds.
  3. (1991). Animal model for dermolytic mechanobullous disease: sheep with recessive dystrophic epidermolysis bullosa lack collagen VII.
  4. (2002). Animal models for skin blistering conditions: absence of laminin 5 causes hereditary junctional mechanobullous disease in the Belgian horse.
  5. (2007). Biological function of laminin-5 and pathogenic impact of its deficieny.
  6. (2005). Epidermolysis bullosa in Assaf lambs.
  7. (2010). Epidermolysis bullosa in German black headed mutton sheep.
  8. (2005). Haploview: analysis and visualization of LD and haplotype maps.
  9. (2005). Inherited junctional epidermolysis bullosa in the German Pointer: Establishment of a large animal model.
  10. (2006). Junctional epidermolysis bullosa in two domestic shorthair kittens.
  11. (2003). L’E ´pidermolyse Bulleuse Jonctionnelle du Braque allemand: un mode `le canin spontane ´ de l’E ´pidermolyse Bulleuse Jonctionnelle de l’Homme. Bull Acad Ve ´t France 157:
  12. (2002). Laminin 5 mutations in junctional epidermolysis bullosa: molecular basis of Herlitz vs. non-Herlitz phenotypes.
  13. (1996). Localization of laminin-5 in the epidermal basement membrane.
  14. (2002). Merlin-rapid analysis of dense genetic maps using sparse gene flow trees.
  15. (1974). Middelberg A
  16. (1997). Non-lethal junctional epidermolysis bullosa in a dog.
  17. (2001). Novel mutations in the LAMC2 gene in non-Herlitz junctional epidermolysis bullosa: effects on laminin-5 assembly, secretion, and deposition.
  18. (2009). Partial deletion of the LAMA3 gene is responsible for hereditary junctional epidermolysis bullosa in the American Saddlebred Horse.
  19. (1992). Pathogenesis of mechanobullous disorders.
  20. (2007). PLINK: a toolset for whole-genome association and population-based linkage analysis.
  21. (2003). Sequence information for the splicing of human pre-mRNA identified by support vector machine classification.
  22. (2001). Short arm region of laminin-5 c2 chain: Structure, mechanism of processing and binding to heparin and proteins.
  23. (2007). TASSEL: software for association mapping of complex traits in diverse samples.
  24. (2008). Widespread and subtle: alternative splicing at shortdistance tandem sites.