title: A frameshift mutation within LAMC2 is responsible for Herlitz type junctional epidermolysis bullosa (HJEB) in black headed mutton sheep.
abstract: 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.
authors.affiliation: Institute for Animal Breeding and Genetics, University of Veterinary Medicine, Hannover, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Mömke
authors.forename: Andrea
authors.initials: A
authors.lastname: Kerkmann
authors.forename: Anne
authors.initials: A
authors.lastname: Wöhlke
authors.forename: Miriam
authors.initials: M
authors.lastname: Ostmeier
authors.forename: Marion
authors.initials: M
authors.lastname: Hewicker-Trautwein
authors.forename: Martin
authors.initials: M
authors.lastname: Ganter
authors.forename: James
authors.initials: J
authors.lastname: Kijas
authors.forename: Ottmar
authors.initials: O
authors.lastname: Distl
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics; D004252:DNA Mutational Analysis; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics*; D007797:Laminin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012756:Sheep; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D007797:Laminin; D000097794:Kalinin; C095567:laminin alpha 3